cloric 0,1 M (TT) lm mu trng. Song song tin hnh vi dung dch papaverin hydroclorid chun c nng khong 4,5 )Lig/ml. Tnh hm lng papaverin hydroclorid, C20H21O4N.HCI, c trong vin da vo hp th ca dung dch th, dung dch chun v hm lng C20H21O4N.HCI ong papaverin hydroclorid.

Bo qunng trong l kn, trnh nh sng.

Loi thucThuc chng co tht.

Hm lng thng dng40 mg.

PARACETAMOLParacetamolum

,NHAc

C8H9NO2 p.t.l: 151,2

Paracetamol l A^-(4-hydroxyphenyl) acetamid, phi cha t 99,0 % n 101,0 % C8H9NO2, tnh theo ch phm lm kh.

Tnh chtBt kt tinh trng, khng mi. Hi tan trong nc, rt kh tan trong clorofonn. ether, imethyien corid, d tan trong dung dch kim, ethanol 96 %.

nh tnhC th chn mt trong hai nhm nh tnh sau:Nhm I: A, c .Nhm II: B, c , D, E.A. Ph hng ngoi (Ph lc 4.2) ca ch phm phi ph hp vi ph hng ngoi ca paracetamol chun.B. Ha tan 0,1 g ch phm ong methanol (TT) v pha long thnh 100,0 ml vi cng dung mi. Ly 1,0 ml dung dch, thm 0,5 ml dung dch acid hydrocloric0,1 M (TT), thm methanol (TT) thnh 100,0 m!. Bo qun dung dch ny trnh nh sng v em o ngay hp th (Ph e 4.1) bc sng cc i 249 nm. A(1 %, 1 cm) phi trong khong 860 n 980.c . im chy (Ph l c l? ) : 168 c n 172 cD. un nng 0,1 g ch phm trong 1 ml acid hydro- coric (TT) trong 3 pht, thm 1 ml nc, lm lnh trong , khng c ta to thnh. Thm 0,05 ml dung dch kai dicromat 0,49 %, xut hin mu tm v khng chuyn sang mu .

E. Ch phm phi c phn ng ca nhm acetyl (Ph lc 8.1). Thc hin phn ng bng cch un trc tip trn la.

Tp cht lin quanXc nh bng phng php sc k lng (Ph lc 5.3). Cc dung dch c chun b ngay khi tin hnh th nghim.Pha ng: Hn hp gm 375 th tch dung dch dinatri hydrophosphat 1,79 %, 375 th tch dung dch natri dihydrophosphat 0,78 % v 250 th tch methanol (TT) c cha 0,46 % ca dung dch tetra-butyamoni hydroxid 40 %.Dung dch th: Ha tan 0,200 g ch phm trong2,5 ml methanol (TI) c cha 0,46 % dung dch tetrabutylamoni hydroxyd 40 % v pha long thnh1 0 . 0 ml vi hn hp ng th tph ca dung dch dinatri hydrophosphat 1,79 % v dung dch natr dihydrophosphat 0,78 %.Dung dch i chiu (1): Pha long 1,0 ml dung dch th thnh 50,0 ml vi pha ng. Pha long 5,0 ml dung dch ny thnh 1 0 0 , 0 ml vi pha ng.Dung dch i chiu (2): Pha long 1,0 ml dung dch i chiu ( 1 ) thnh 1 0 , 0 ml vi pha ng.Dung dch i chiu (3): Ha tan 5,0 mg 4-aminophenol (TT), 5 mg paracetamol chun v 5,0 mg cloroacetanilid (71) trong methanol (FT) v pha long thnh 20,0 ml vi cng dung mi. Pha long 1,0 ml dung dch ny thnh250.0 ml vi pha ng.Dung dch i chiu (4): Ha tan 20,0 mg 4-ntrophenol (TT) ong methanol (TT) v pha long thnh 50,0 ml vi cng dung mi. Pha long 1,0 ml dung dch ny thnh2 0 . 0 ml vi pha ng.iu kin sc k:C t th p k h n g g i ( 2 5 c m X 4 ,6 m m ) c n h i p h a

tnh B (5 |xm). Duy tr nhit ct 35 c Tc dng: 1,5 ml/minDetector quang ph t ngoi bc sng 245 nm Th tch tim: 20 1^ 1.Cch tin hnh: Tim cc dung dch i chiu.Ly paracetamol lm i chiu (thi gian lu khong4 pht): Thi gian lu tng i ca tp cht K khong 0,8; tp cht F khong 3; tp cht J khong 7. Php th ch c gi tr khi trn sc k ca dung dch i chiu (3): phn gii gia pic ca tp cht K v pic ca paracetamol t nht l 4;T l gia tn hiu v nhiu cho pic ca tp cht J t nht l 50.Tim dung dch th v tin hnh chy sc k vi thi gian gp 1 2 ln thi gian lu ca pic paracetamol.Trn sc k ca dung dch th:

Din tch pic tp cht J: khng gu 0,2 n din tch ca pic tng ng trn sc k thu c ca dung dch i chiu (3) (10 phn triu)Din tch pic tp cht K: khng ln hn din tch ca pic tng ng trn sc k thu c ca dung dch i chiu (3) (50 phn triu).Din tch pic tp cht F: khng ln hn 0,5 ln din tch ca pic tng ng n sc k thu c ca dung dch i chiu (4) (0,05 %).Din tch pic ca bt k tp cht no khc: khng ln hn 0,5 ln din tch ca pic chnh trn sc k thu c ca dung dch i chiu (1) (0,05 %).Tng din tch pic ca cc tp cht khc: khng ln hn din tch ca pic tng ng trn sc k thu c ca dung dch i chiu ( 1 ) (0 , 1 %).

B qua cc pic c din tch nh hn din tch ca pic chnh trn sc k thu c ca dung dch i chiu (2) (0,01 %).Ghi ch:Tp cht A: iV-(2-hydroxyphenyl)acetamidTp cht B: A^-(4-hydroxyphenyl)propanamidTp cht C: A^-(3-cloro-4-hydroxyphenyl)acetamidTp cht D: A^-phenylacetamidTp cht E: l-(4-hydroxyphenyl)ethanonTp cht F: 4-nitrophenolTp cht G: 1 -(4-hydroxyphenyl)ethanon oximTp cht H: 4-(acetylamino)phenyl acetatTp cht I: 1 -(2-hydroxyphenyl)ethanonTp cht J: iV-(4-clorophenyl)acetamid (cloroacetanilid)Tp cht K: 4-aminophenol.

1. Tp cht K 5. Tp cht c 9. Tp cht F2. Paracetamol 6 . Cc tp cht E v D 10. Tp cht I3. Tp cht B 7. Tp cht G 11. Tp cht J4. Tp cht A 8 . Tp cht H

Hnh 1. Sc k ca th nghim cc tp cht lin quan

Kim loi nngKhng c qu 20 phn triu (Ph lc 9.4.8).Ha tan 1,0 g ch phm trong hn hp nc - aceton (15 : 85) ri pha long thnh 20,0 m bng cng hn hp dung mi. Ly 12 ml dung dich ny th theo phng php 2. Dng dung dch ch mu 1 phn triu thu c bng cch pha long dung dch ch mu 100 phn triu (TT) vi hn hp dung mi n chun b mu i chiu.

Mt khi lng do lm kfiKhng c qu 0,5 % (Ph lc 9.6).Dng 1,000 g ch phm; sy 100 c n 105 c.

Tro SulfatKhng c qu 0,1 % (Ph lc 9.9, phong php 2). Dng 1,0 g ch phm.

nh lngHa tan 0,300 g ch phm trong hn hp gm 10 ml nirc v 30 ml dung dch acid sulfuric long (TT). un si hi lu trong 1 gi, !m lnh v pha long thnh 100,0 ml bng nc. Ly 20,0 ml dung dch, thm 40 ml nc, 40 g nc , 15 ml dung dch acid hydrocloric long (TT) v 0,1 ml dung dch, feroin (TT). nh lng bng dtmg dch amoni cer Sulfat 0,1 M (C) cho n khi xut hin mu vng xanh. Song song tin hnh mu trng trong cng iu kin.1 ml dung dch amoni ceri Sulfat 0,1 M (C) tng ong vi 7,56 mg C8H9NO2 .

Bo qunTrong l kn, trnh nh sng.

Loi thucH st, gim au.

Ch phmVin nn, vin bao phii, hn dch ung, dung dch ung, vin nn si bt.

NANG PARACETAMOL Capsulae Paracetamoli

L nang cng cha paracetamol.Ch phm phi p ng cc yu cu ong chuyn lun Thuc nang (Ph lc 1.13) v cc yu cu sau:

Hm lng paracetamol, C8H9NO2, t 95,0 % n105,0 % so vi lng ghi trn nhn.

Tnh chtNang cng bn trong cha bt thuc mu trng, khng mi.

nh tnhA. Ly mt lng bt thuc tng ng vi khong 0,5 g paracetamol, thm 30 ml aceton (TT), khuy k,

lc, lm bay hi dch lc n cn, ly cn lm cc phn ng sau y:un si 0,1 g cn vi 1 ml acid hydrocloric (TT) trong 3 pht, thm 10 ml nc ct, ngui. Thm 1 git dung dch kali dcromat 5 % (TT) s xut hin mu tm, khng chuyn sang mu .Sy cn 105 c, chy ca cn khong 168 c n 172 c (Ph lc 6.7).B. Sc k lp mng (Ph lc 5.4).B n m n g: S ilic a g e l GF254.Dung mi khai trin: Methylen clord - methanol (4 : 1). Dung dch th: Ha tan mt lng bt thuc trong nang tng ng vi 1 0 mg paracetamol trong 1 0 ml methanol (TT). ^Lc. ^Dung dch i chiu: Ha tan 10 mg paracetamol chun trong 10 ml methanol (TT).Cch tin hnh: Chm ring bit ln bn mng 20 |J.I cc dung dc h trn. Trin khai sc k n khi dung mi i c 15 cm. Ly bn mng ra kh ngoi khng kh. Quan st di nh sng t ngoi bc sng 254 nm. v t chnh thu c trn sc k ca dung dch th phi tng ng v v tr kch thc v mu sc vi vt chnh thu c trong sc k ca dung dch i chiu.

ha tan (Ph lc 11.4)Thit b: Kiu cnh khuy.Mi trng ha tam 900 m \m phosphatpH 5,8.Tc quay: 50 r/min. '----Thi giam 45 min.Cch tin hnh: Ly mt phn dung dich mi ng sau khi ha tan, lc, b dch lc u. Pha long dch lc bang dung dch natri hydroxyd 0,1 M(TT) c dung dch c nng paracetamol khong 7,5 ^g/ml. o hp th (Ph lc 4.1) ca dung dch thu c bc sng cc i 25,7 nm, mu trng l dung dch ncri hydroxyd 0,1 M (TT). Tnh hm lng paracetamol ha tan theo A (1 %,1 cm). Ly 715 l gi tr A (1 %, 1 cm) ca paracetamol bc sng 257 nm.Yu cu: Khng c di^75 % lng paracetamol, C8H9NO2, so vi lng ghi trn nhn c ha tan trong 45 pht.

Kiong c qua 0 , 1 %.Tin hnh bng phong php sc k lng (Ph lc 5.3). Pha ng: D m g dch nairi butansulfonat 0,01 trong hn hp acidformic - methanol - nc (0,4 : 15 : 85). Dung dch chun: Cha 0,001 % 4-aminophenol trong methanol 15 %.Dung dch th: Lc mt lng bt thuc trong nang tcmg ng 1,0 g paracetamol trong 15 ml methanol (TT), thm nc va 100 ml v ic.iu kin sc k:C t th p k h n g g ( 2 5 c m X 4 ,6 m m ) c n h i p h a

tnh c (10 im).

Detector quang ph t ngoi t bc sng 272 nm. Tc dng: 2 ml/min.Th tch tim: 20 xl.Cch tin hnh: Tim ln lt dung dch chun v dung dch th. Trn sc k thu c t dung dch th, pic tng ng vi 4-aminophenol khng c c din tch ln hn din tch pic 4-aminophenol thu c trn sc k ca dung dch chun (0 , 1 %).

Tp cht lin quanPhng php sc k lp mng (Ph lc 5.4).Bn mng: Silica gel GF254.Dung mi khai trin: Toluen - aceton - cloroorm (10 ; 25:65).Dung dch th (1): Ly mt lfng bt thuc trong nang tng ng vi 1 , 0 g paracetamol vo ng ly tm c np, thm chnh xc 5 ml ether khng c peroxyd (77), y np, lc c hc 30 pht. Ly tm vi tc 1000 r/min trong khong 15 pht hoc cho n khi thu c durg dch hon ton trong.Dung dch th (2): Ly chnh xc 1 ml dung dch th(1) pha lohg va vi 10 ml ethanol 96 % T). Dung dch i chiu (1): Cha 0,0050 % 4'-cloroace- tanilid trong ethanol 96 % (TT).Dung dch i chiu (2): Ha tan 0,25 g 4'-cloroace- tanilid v 0 , 1 g paracetamol va 1 0 0 m vi ethanol 96 % (TT).Cch tin hnh:Chm ring bit ln bn mng cc dung dch trn nh sau: 200 |Lil dung dch th (1), 40 |J,1 dung dch th (2), dung dch i chiu ( 1 ) v dung dch i chiu (2 ). Cho dung mi khai trin vo bnh sc k khng lt giy v t ngay bn mng va chm cc dung dch vo bnh. Trin khai sc k cho n khi dung mi i c khong 14 cm. Sau khi trin khai, bn mng kh hon ton, quan st di sng t ngoi bc sng 254 nm. Bt k vt no trn sc k ca dung dch th (1) tng ng vi vt ca 4'-cloroacetanilid khng c m hn vt trn sc k ca dung dch i chiu ( 1 ).Bt k vt ph no trn sc k ca dung dch th(2), c gi tr Rf thp hn gi tr Rf ca 4'-cloroa- cetanilid khng c m hn vt trn sc k ca dung dch i chiu ( 1 ).Th nghim ch c gi tr khi trn sc k dung dch i chiu (2 ) c 2 vt tch ra r rng, vt tng ng vi 4'-cloroacetanilid phi c gi tr Rf cao hn.

nh lngCn 20 nang, tnh khi lng trung bnh ca bt thuc trong mt nang v nghin thnh bt mn. Cn chnh xc mt lng bt thuc tng ng vi khong 0,150 g paracetamol vo bnh nh mc 200 ml, thm 50 ml dung dch natri hydroxyd 0,1 M (TI), thm 100 ml nc, lc 15 pht. Thm nc n nh mc. Lc u.

lc. Loi b 10 ml ch lc u. Ly chnh xc 10 ml dch lc cho vo bnh nh mc 1 0 0 ml, pha long vi nc n nh mc, lc u. Ly chnh xc 10 ml dung dch ny cho vo bnh nh mc 1 0 0 ml khc, thm 10 ml dung dch natri hydroxyd 0,1 M (TT), pha long vi nc n nh mc, lc u. o hp th (Ph lc 4.1) ca dung dch thu c bc sng 257 nm, cc dy 1 cm. Dng dung dch natri hydroxyd 0,01 M (TT) lm mu trng.Tnh hm lng paracetamol, C8H9NO2, theo A (1 %, 1 cm). Ly 715 l gi tr A (1 %, 1 cm) bc sng 257 nm.

Bo qune ni mt, trong ng kn, trnh nh sng.

Loi thucH st, gim au.

Hm lng thng dng 500 mg.

VIN T PARACETAMOL Suppositoria ParacetamoliL vin t cha paracetamol.Ch phm phi p ng cc yu cu trong chuyn lun Thuc t (Ph lc 1.10) v cc yu cu sau y:

Hm lng paracetamol, C8H9NO2, t 95,0 % n105,0 % so vi lng ghi trn nhn.

Tnh chtVin t c hnh dng thch hp t trc trng.

nh tnhA. Tin hnh bng phng php sc k lp mng (Ph lc 5.4).Bn mng: Silica gel GF254.Dung mi khai trin: Methanol - dicloromethan (1 : 4) Dung dch th: Ly 1 vin ch phm, thm mt th tch methanol (TT) thch hp thu c dung dch c nng paracetamol 0,1 %. t trn cch thy cho n khi ch phm tan, ngui, thnh thong khuy, lc.Dung dch i chiu: Dung dch paracetamol chun 0,1 % trong methanol (TT).Cch tin hnh: Chm ring bit ln bn mng 10 p.1 mi dung dch trn. Trin khai sc k n khi dung mi i c khong 1 0 cm, ly bn mng ra kh ngoi khng kh. Quan st di nh sng t ngoi 254 nm. v t chnh n sc k ca dung dch th phi tong ng v v tr, kch thc v mu sc vi vt chnh trn sc k ca dung dch i chiu.B. Cn mt lng thuc tng ng khong 50 mg paracetamol, ct nh, thm 1 ml acid hydrocloric (TT)

v un n si trong 3 pht, thm 10 ml nc, ngui khng to kt ta. Thm 0,05 ml dung dch kali dicromat (TT), xut hin mu tm khng chuyn sang .

4-aminophenoITin hnh bng phoTig php sc k lng (Ph lc5.3).Pha ng: Dung dch natri butansulfonat 0,01 M trong hn hp acidformic - methanol - nc (0,4 : 15 ; 85). Dung dch chun: Dung dch 4-aminophenol 0,0005 % trong pha ng.Dung dch th: Ly mt lng ch phm trong s nm vin c ct nh, ha tan trong lng ti thiu ethanol 96 % (TT), lm m nu cn, lc cho tan ri pha long vi nc c dung dch c nng khong 0,5 % paracetamol.iu kin sc k:C t th p k h n g g (2 5 c m X 4 ,6 m m ) c n h i p h a

tnh c (10Detector quang ph t ngoi t bc sng 272 nm. Tc dng: 2 ml/min.Th tch tim: 20 (4,1.Cch tin hnh: Tim ln lt dung dch chun v dung dch th. Trn sc k thu c t dung dch th, pic tng ng vi 4-aminophenol khng c c din tch ln hn din tch pic 4-aminophenol thu c trn sc k ca dung dch chun (0 , 1 %).

nh lngVin t c cha hot cht ln hn 150 mg:Ly mt vin, thm 30 ml nc v 100 ml dung dch acid sulfuric 1 M (TT). un hi lu trong 1 gi, ngui, thm 100 ml nc, 50 g nc (ng lnh t nc ct), 50 ml dung dch acid hydrocloric long (TT)yk 0,2 ml dung dch feroin sulfat (TT).Chun bng dung dch amon ceri suat 0,2 M (C) cho n khi xut hin mu vng.1 ml dung dch amoni ceri sulfat 0,2 M (C) tng ng 15,12 mg paracetamol, CgHNOa- Lp li php th trn bn vin khc. Tnh hm lng trung bnh ca mt vin.Vin t c cha hot cht nh hn hoc bng 150 mg:Ly mt vin thm 10 ml nc v 30 ml dung dch acid sulfuric long (TT). un hi lu trong 1 gi, ngui, thm 40 ml nc, 40 g nc (ng lnh t nc ct), 15 ml dung dch acid hydroclorc long (TT) v 0,1 ml dung dch feroin sulfat (TT).Chun bng dung dch amoni cer sulfat 0,1 M (C) cho n khi xut hin mu vng.1 ml dung dch amoni cer suat 0,1 M (C) tng ng vi 7,56 mg C8H9NO2 .Lp li php th trn bn vin khc. Tnh hm lng trung bnh ca mt vin.

Bo qunTrong bao b kn, nhit t 4 c n 8 G.Loi thucGim au, h st.

Hm lng thng dng500 mg.

VIN NN PARACETAMOL Tabellae ParacetamoliL vin nn cha paracetamol.Ch phm phi p ng cc yu cu trong chuyn lun Thuc vin nn (Ph lc 1.20) v cc yu cu sau y:

Hm lng ca paracetamol, C8H9NO2,i vi vin 100 mg: T 90,0 % n 110,0 % so vi lng ghi trn nhn.i vi vin 300 mg v 500 mg: t 95,0 % n 105,0 % so vi lng ghi trn nhn.

Tnh chtVin mu trng, khng mi.

nh tnhCh phm phi p ng cc yu cu nh tnh trong chuyn lun Nang paracetamol thay bt thuc trong nang bng bt vin.

ha tan (Ph lc 11.4)Ch phm phi p ng yu cu v php th ha tan trong chuyn lun Nang paracetamol.

4-AminophenoICh phm phi p ng yu cu v php th 4- Aminophenol trong chuyn lun Nang paracetamol thay bt thuc trong nang bng bt vin.

Tp cht lin quanCh phm phi p ng yu cu v php th Tp cht lin quan trong chuyn lun Nang paracetamol thay bt thuc trong nang bng bt vin.

nh l n gCn 20 vin, tnh khi lng trung bnh vin v nghin thnh bt mn. Cn chnh xc mt lng bt vin tng ng khong 0,15 g paracetamo vo bnh nh mc 200 ml, thm 50 ml dung dch natri hydroxyd 0,1 M (TT) v 100 ml nirc, lc ] 5 pht, thm nc n nh m cL c u, lc qua giy lc kh, b 2 0 ml dch lc u.)Ly chnh xc 1 0 ml dch lc cho vo bnh nh mc 100 ml. Thm nc va n vch, lc u y Ly chnh xc 10 ml dung dch n cho vo bnh nh mc 1 0 0 ml, thm 1 0 ml dung dch nar hydroxyd 0,1 M (77), thm nc n nh mc, lc u. o hp th (Ph lc 4.1) ca dung dch thu c bc sng 2 ^ nm, dng cc dy 1 cm. Mu ng l dm g dch natri hydroxyd 0,01 M (TT).

Tnh hm ing paracetamol, CsHNOi theo A ( 1 %, 1 cm). Ly 715 l gi tr A (1 %, 1 cm) bc sng 257 nm.

Bo qun ni mt, trong ng kn.

Loi thucGim au, h st.

Hm lng thng dng100 mg, 300 mg, 500 mgr

VIN SI PARACETAMOL Effervescents abellae Paracetamoli

L vin nn si cha paracetamol.Ch phm phi p ng cc yu cu ca vin si trong chuyn lun Thuc vin nn mc Vin si bt (Ph lc 1.20) v cc yu cu sau y:

Hm lng paracetamol, CgHNOa, t 95,0 % n105,0 % so vi lng ghi trn nhn.

Tnh chtVin nn mu trng.

nh tnhA. Ha tan vin vi nc m, sau khi vin ht si bt, dung dch thu c phi hi c.B. o ph hp th t ngoi (Ph lc 4.1) phn nh lng trong khong bc sng t 230 nm n 350 nm. Ph thu c phi c cc i hp th bc sng 257 nm,c . Trong phn th Tp cht lin quan, vt chnh thu c trn sc k ca dung dch th (3) phi tng ng v v tr, kch thc, mu sc vi vt thu c trn sc k ca dung dch i chiu (3).

4-aminophenolKhng c qu 0,1 %.Tin hnh th nh m t trong chuyn lun Nang paracetamol, thay bt thuc trong nang bng bt vin.Tp cht lin quanTin hnh bng phng php sc k lp mng (Ph lc 5.4).Bn mng-. Silica gel Gp254.Dung mi khai trin'. Toluen - aceton - cloro/orm (10 : 25 : 65)Dung dch th (1): Ly mt lng bt vin tng ng vi 1 , 0 g paracetamol, cho vo ng ly tm c np, thm vo 10 ml ether khng c peroxyd (77), y np, lc c hc 30 pht. Ly tm vi vn tc 1000 r/min khong 15 pht hoc cho n khi thu c lp dung dch pha trn hon ton trong. S dng lp dung dch ny.Dung dch th (2): Pha long 1 ml dung dch (1) thnh 10 ml vi ethanol 96 % (TT).

Dung dch th (3)\ Ly mt lng bt vin tng ng vi 0 , 1 g paracetamol ha tan va vi 1 0 0 ml ethanol 96 % (TT).Dung dch i chiu (1): Dung dch cha 0,0025 % (kl/tt) 4'-cloroacetanilid trong ethanol 96 % (TT).Dung dch i chiu (2): Ha tan 0,25 g 4'-cloroace- tanilid v 0 , 1 g paracetamol chun va vi 1 0 0 ml ethanol 96 % (TT).Dung dch i chiu (3): Dung dch c cha 0,1 % paracetamol chun trong ethanol 96 % (TT).Cch tin hnh:Chm ring bit ln bn mng cc ung dch trn nh sau: 200 p,l dung dch th ( 1 ) ; 40 |J.I mi dung dch th (2 ), dung dch i chiu (]), dung dch i chiu(2 ), dung dch th (3), dung dch i chiu (3). Cho dung mi khai trin vo binh sc k khng lt giy v t ngay bn mng va chm cc dung dch vo bnh. Trin khai sc k n khi dung mi i c 15 cm. Ly bn mng ra kh hon ton nhit phng. Quan st di nh sng t ngoi bc sng 254 nm. Bt k vt no trn sc k thu c t dung dch th (1) tng ng vi vt ca 4'-cloroacetanilid cng khng c m hn vt trn sc k dung dch i chiu (1) (0,005 %).Bt k vt ph no trn sc k ca dung dch th(2) c gi tr Rf thp hn gi tr Rf ca 4'-cloroa- cetanilid khng c m hn vt trn sc k dung dch i chiu (1) (0,25 %).Loi b bt c vt ph no nm ti vch hay ngay trn vch chm sc k.Th nghim ch c gi tr khi trn sc k dung dch i chiu (2 ) cho hai vt tch r rng ring bit, vt tng ng vi 4'-cloroacetanilid phi c gi tr Rf cao hn.

nh lngCn 20 vin, tnh khi lng trung bnh vin v nghin thnh bt mn. Cn chnh xc mt lng bt vin tng ng vi khong 0,150 g paracetamol cho vo bnh nh mc 2 0 0 ml, thm 50 ml dung dch natr hydroxyd 0,1 M T) v ch cho dung dch ht si bt, thm 100 m nc, lc k 15 pht. Thm nc n nh mc, lc u. Lc, loi b 20 ml dch lc u. Pha long 10,0 ml dch lc thnh 100,0 ml vi nc. Ly chnh xc 10 ml dung dch ny cho vo bnh nh mc th tch 1 0 0 ml, thm 1 0 ml dung dch natri hydroxyd 0,1 M (TT). Pha long vi nirc n nh mc. o hp th nh sng (Ph lc 4.1) ca dung dch thu c bc sng 257 nm, cc o dy 1 cm. Dng dung dch natri hydroxyd 0,01 M (TT) lm mu trng. Tnh hm lng paracetamol (CgHNOa) theo A ( 1 %, 1 cm). Ly 715 l gi tr A (1 %, Icm), bc sng 257 nm.

Bo qun ni mt, trong irng kn, trnh nh sng.

Loi thucGim au, h st.

Hm lng thng dng500 mg.

VIN NN PARACETAMOL V CAFEIN Tabellae Paracetamoli et Coffeini

L vin nn cha paracetamol v cafein.Ch phm phi p ng cc yu cu trong chuyn lun Thuc vin nr (Ph lc 1.20) v cc yu cu sau y:

Hm lng paracetamol, C8H9NO2, v cafein,O8H10N4O2, t 90,0 % n 110,0 % so vi lng ghi trn nhn.

Tnh chtVin nn mu trng.

nh tnhTrong phn nh lng, thi gian lu tng i ca cc pic chnh paracetamol v cafein so vi pic chun ni trn sc k thu c ca dung dch th v dung dch chun phi ph hp vi nhau.

ha tan (Ph lc 11.4)Thit b: Kiu cnh khuy.Mi trng ha tan: 900 ml mtc.Tc quay: 100 r/min.Thi gian: 60 min.Pha ng, dung dch chun ni, hn hp dung mi, dung dch chun gc, iu kin sc k v cch tin hnh thc hin nh m t trong phn nh lng. Dung dch chun: Ht chnh xc 20,0 ml dung dch chun gc vo bnh nh mc 50 ml, thm chnh xc3,0 ml dung dch chun hi v 20 m nc, trn u, yn khong 30 giy. Pha long bng hn hp dung mi n nh mc, trn u. Dung dch ny s dng trong vng 8 gi.Dung dch th: Ly mt phn dung dch mi trng sau khi ha tan, lc, b 20 ml dch lc u. Ly mt th tch chnh xc dch lc cho vo binh nh mc 50 ml sao cho dung dch thu c c nng paracetamol 0 , 1 mg/ml v nng cafein 0 ,iy mg/ml, Jc xc nh dung dch chun gc. Thm chnh xc 3,0 ml dung dch chun ni v 20 ml hn hp dung mi, trn u, yn khong 30 giy. Pha long bng hn hp dung mi n nh mc, trn u.Tnh hm lng ca paracetamol, C8H9NO2, v cafein, C8H10N4O2, ha tan trong mi vin t t s gia din tch pic paracetamol hoc cafein v din tch pic chun ni trn sc k ca dung dch th, dung dch cun v nng paracetamol v cafein trong dung ch chun.

Yu cu: Khng c t hn 75 % lng paracetamol, C8H9NO2, v cafein, C8H10N4O2, so vi lng ghi trn nhn c ha tan trong 60 pht.

nh lngTin hnh bng phng php sc k lng (Ph lc 5.3). Pha ng: Nc - methanol - acid acetic bng (69 : 28 : 3), iu chnh t l nu cn.Dung dch chun ni: Chun b dung dch acid benzoic trong methanol (TT) c nng khong 6 mg/ml.Hn hp dung mi: Methanol - acid acetic bng (95 : 5). Dung dch chun gc: Ha tan chnh xc mt lng paracetamol chun v cafein chun trong hn hp dung mi thu c dung dch c nng 0,25 mg/ml ca paracetamol v 0,25J mg/ml ca cafein, / l t l lng ghi trn nhn ca cafein v lng ghi trn nhn ca paracetamol trong vin.Dung dch chun: Ht chnh xc 20,0 ml dung dch chun gc v 3,0 m dung dch chun ni vo binh nh mc 50 ml, pha long bng hn hp dung mi n nh mc, trn u. Dung dch thu c c nng paracetamol khong 0 , 1 mg/ml v nng cafein khong 0 , 1 Jmg/ml.Dung dch th: Cn 20 vin, tnh khi lng trung binh vin, nghin thnh bt mn. Cn chnh xc mt lng bt vin tng ng khong 250 mg paracetamol vo bnh nh mc 100 ml, thm khong 75 ml hn hp dung mi, lc trn my lc 30 pht. Pha long bng hn hp dung mi n nh mc, trn u. Ht chnh xc 2,0 ml dung dch ny v 3,0 ml ung dch chun ni vo binh nh mc 50 ml, pha long bng hn hp dung mi n nh mc, trn u.u kin sc k:Ct thp khng g (10 cm X 4^6 lim) c nhi pha tnh c (5 |Lim).Nhit ct: 45 c 1 ^c.Detector quang ph t ngoi t bc sng 275 nm. Tc dng: 2 ml/min.Th tch tim: 10 |liL Cch tin hnh:Kim tra kh nng thch hp ca h thng sc k: Tin hnh sc k vi dung dch chun. H s i xng ca pic tng ng vi paracetamol v cafein khng c ln hn 1,2. phn gii gia pic tng ng vi paracetamol, cafein v pic chun ni khng c nh hn 1,4. lch chun tng i ca cc din tch p ng t 6 ln tim lp li khng c ln hn 2,0 %.Tin hnh sc k ln lt vi dung dch chun v dung dch th. Thi gian lu tong i ca paracetamol khong 0,3, ca cafein khong 0,5 v ca acid benzoic l 1 ,0 .Cn c vo din tch pic thu c t dung dch th, dung dch chun v da vo hm lng C8H9NO2 ca paracetamol chun v C8H 10N4O2 ca cafein chun,

tnh hm lng paracetamol C8H9NO2, v cafein, C8H10N4O2, c trong mt n v ch phm t t s gia din tch pic paracetamol hoc cafein v din tch pic cht chun ni trn sc k ca dung dch th, dung dch chun v nng paracetamol v cafein trong dung dch chun.

Bo qunTrong bao b kn nhit t 15 c n 30 c.Loi thucGim au, h st.

Hm lng thng dng200 mg paracetamol, 50 mg cafein.500 mg paracetamol, 65 mg cafein.

VIN NN PARACETAMOL VCLORPHENIRAMINTabellae Paracetamoli et ChlorpheniraminiL vin nn cha paracetamol v clorpheniramin maleat.Ch phm phi p ng cc yu cu ong chuyn lun Thuc vin nn (Ph lc 1.20) v cc yu cu sau y:

Hm lng paracetamol, CgHgNOi, t 90,0 % n1 1 0 , 0 % so vi lTig ghi trn nhn.

Hm lng clorpheniramin maleat,C 16H19CN2 .C4H4O4, t 90,0 % n 110,0 % so vi lng ghi trn nhn.

Tnh chtVin nn mu ng u.

nh tnhA. Trong phn nh lng paracetamol, thi gian lu ca pic chnh t sc k ca dung dch th phi tng ng vi thi gian lu ca pic paracetamol n se k ca dung dch chun.B. Trong phn nh lng cloqjheniramin maleat, thi gian lu ca pic chnh n sc k ca dung dch th phi tng ng vi thi gian lu ca pic clorpheniramin maleat n sc k ca dung dch chun.

ha tan (Ph lc 11.4)Thit b. Kiu cnh khuy.Mi trng ha tam 900 ml nc.Tc quy: S rlmn.Thi gian: A) mm.Cch tin hnh. Ly mt phn dung dch mi trng sau khi ha tan, lc, b dch lc u. Pha long dch lc bng dung dch natri hydroxyd 0,1 M (TT) c dung dch c nng paracetamol khong 7,5 ^ig/ml. o hp th (Ph lc 4.1) ca dung dch thu c bc sng cc i 257 nm, mu trng l dung dch

natri hydroxyd 0,1 M (TT). Tnh hm lTig paracetamol ha tan theo A (1 %, 1 cm). Ly 715 l gi tr A (1 %, 1 cm) ca paracetamol bc sng 257 nm.Yu c. Khng c di 75 % lng paracetamol, C8H9NO2, so vi lng ghi trn nhn c ha tan trong 45 pht.

nh lng paracetamolTin hnh bng phng php sc k lng (Ph lc5.3).Fha ng: Nc - methanol - acid acetic bng (79 : 2 0 : 1), iu chnh t l nu cn.Dung dch chun: Cn chnh xc khong 50 mg paracetamol chun vo bnh nh mc 100 ml, thm 4 ml methanol (TT), lc cho tan hon ton, pha long vi dung dch acid phosphoric 1 % (TT) n nh mc, trn u.Dung dch th: Cr 20 vin, tnh khi lng trung bnh vin v nghin thnh bt mn. Cn chnh xc mt lng bt vin tng ng vi khong lO mg paracetamol vo bnh nh mc 50 ml, thm khong1,5 xn\ methanol (TT), siu m cho bt phn tn hon ton, thm 0,5 ml acid phosphoric (TT), pha long vi nc n nh mc, trn u. Ht 25,0 ml dch lc cho vo bnh nh mc 1 0 0 ml, pha long vi nc n nh mc, trn u.iu kin sc k:Ct thp khng g (15 cm X 4,6 mm) c nhi pha tnh B (octylsilyl silica gel, ht 5 |j,m n 10 |j,m). Detector quang ph t ngoi t bc sng 280 nm. Tc dng: 1 ml/min.Th tch tim: 10 fj,l.Cch tin hnh:Kim tra tnh thch hp ca h thng sc k; Tin hnh sc k vi dung dch chun, h s i xng ca pic paracetamol khng c ln hn 2 , 0 v lch chun tong i c cc din tch pic p ng t 6 ln tim lp li khng qu 2 , 0 %.Tin hnh sc k ln lt vi dung dch chun v dung dch th.Tnh hm lng paracetamol, C8H9NO2, c trong vin da vo din tch pic trn sc k thu c t ung dch th, dung dch chun v hm lng CgHNOa ca paracetamol chun.

nh lng clorpheniramin maleatTin hnh phng php sc k lng (Ph lc 5.3).Pha ng: Hn hp methanol - nc (60 : 40) c cha 0,34 g kai dihydrophosphat (TT)', 0,3 % iethylamin hydroclorid (TT); 0,15 g nai aurylsuat (TT) v 0,1 ml acid phosphoric (TT) ong mi 100 ml dung dch, iu chnh t l nu cn.Dung dch chun: Cn chnh xc v ha tan ong nc mt lng clorpheniramin maleat chun thu c dung dch c nng khong 0,8 mg/ml. Tip

tc pha long dung dch ny bng dung dch acid phosphoric 0,1 % (TT) thu c dung dch c nng khong 8 Jig/ml.Dung dch th: Cn 20 vin, tnh khi lng trung bnh vin v nghin thnh bt mn. Cn chnh xc mt lng bt vin tng ng vi khong 2 mg clorphe- niramin maleat vo bnh nh mc 250 ml, thm 25 ml methanol (TT), siu m cho bt phn tn hon ton, thm 1 ml acid phosphoric (TT), pha long vi nc va n vch, trn u.iu kin sc k:Ct thp khng g (15 cm X 4,6 mm) c nhi pha tnh silica lin kt vi cc nhm phenyl (ht 5 |xm n 1 0 |um).Deteetor quang ph t ngoi t bc sng 214 nm. Tc dng: 2 ml/min.Th tch tim: 10 f0,l.Kim tra tnh thch hp ca h thng sc k: Tin hnh sc k vi dung dch chun, h s i xng ca pic clorpheniramin maleat khng c ln hn 2 , 0 v lch chun tng i ca cc din tch pic p ng t 6 ln tim lp li khng qu 2 , 0 %.Tin hnh sc k ln lt vi dung dch chun v dung dch th.Tnh hm , lng clorpheniramin maleat, C16H19CIN2.C4H4O4, c trong vin da vo din tch pic n sc k thu c t dung dch th, dung dch chun v hm lng C16H19CIN2.C4H4O4 ca clorpheniramin maleat chun.i vi vin phi th ng u hm lng, ly kt qu nh lng trung bnh ca 1 0 vin lm kt qu nh lng.

ng u hm lngCh phm c lng clorpheniramin maleat di 2 mg trong 1 vin hoc di 2 % khi lng vin phi t yu cu v ng u hm lng i vi clorpheniramin maleat (Ph lc 11.2).Tin hnh phng php sc k lng (Ph lc 5.3)Pha ng, iu kin sc k, cch tin hnh nh m t trong mc nh lng clorpheniramin maleat.Dung dch th. Ly 1 vin nghin thnh bt mn ri chuyn vo bnh nh mc 250 ml, thm 25 ral methanol (TT), siu m cho bt phn tn hon ton, thm 1 ml acidphosphoric (77), pha long vi nc va n vch, trn u.Dung dch chun: Tin hnh nh m t ong mc nh lng clorpheniramin maleat. Pha long (nu cn) c c nng clorpheniramin maleat tng ng vi nng clorpheniramin maleat trong dung dch th.Tnh hm lng clorpheniramin maleat, C16H19CIN2.C4H4O4, trong mt vin da vo din tch pic trn sc k thu c tr dung dch th, dung dch chun v hm lng C 16H19CIN2 .C4H4O4 ca clorpheniramin maleat chun.

Bo qunTrong bao b kn, nhit t 15 c n 30 c.Loi thucThuc gim au, khng histamin.

Hm lng thng dng500 mg paracetamol; 4 mg hoc 2 mg clorpheniramin malea.

VIN NN PARACETAMOL V GODEIN PHOSPHATTabellae Paracetamoli et Codein phosphas

L vin nn cha paracetamol v codein phosphat.Ch phm phi p ng cc yu cu frong chuyn lun Thuc vin nn (Ph lc 1.20) v cc yu cu sau y:

Hm lng paracetamol, CgHNO, t 90,0 % n1 1 0 , 0 % so vi lng ghi trn nhn

Hm lng codein phosphat hemihydrat,C,8H2iN0 3 7 H3P0 4 .'/2H2 0 , t 90,0 % n 110,0 % so vi lng ghi trn nhn.

Tnh chtVin nn mu trng.

nh tnhA. Trong phn nh lng, thi gian lu ca hai pic chnh trn sc k ca dung dch tlj phi tng ng vi thi gian lu ca pic paracetamol v pic codein phosphat thu c frn sc k ca dung dch chun.B. Phng php sc k lp mng (Ph lc 5.4)Bn mng: Silica gel GF254Dung mi khai trin: Methanol - amoniac (49 : 1). Dung dch th: Ly mt lng bt vin tng ng khong 1 2 mg codein phosphat cho vo bnh chit, thm 5 ml nc, 1 ml amoniac (TT) v 5 ml methylen clorid (TI), lc 1 pht, yn cho tch lp, s dng lp dung dch di lm dung dch th.Dung dch i chiu: Pha dung dch codein phosphat chun v paracetamol chun trong methylen clorid T) thu c dung dch c nng tng ng vi nng codein phosphat v paracetamol trong dung dch th.Cch tin hnh: Chm ring bit ln bn mng 10 |LiI' mi dung dch th v dung dch i chiu.Trin khai sc k n khi dung mi i c 3/4 bn mng, ly bn mng ra, kh t nhin v quan st di nh sng t n^oi bc sng 254 nm. Hai vt chnh trn sc k o ca dung dch th phi c v tr v kch thc ton ng vi hai vt chnh trn sc k ca dung dch oi chiu.

ha tan (Ph lc 11.4)Tht b: Kiu cnh khuy.

Mi trng ha tan: 900 m dung dch acid hydro- cloric 0,01 M(TT).Tc quay: Srlrmn.Thi gian:'iO mm.Cch tin hnh'.Dung dch th: Ly mt phn dung dch mi trng sau khi ha tan, lc, b dch c u. Xc nh hm lng paracetamol CgHNO v codein phosphat hemihydrat C 18H21NO3 .H3PO4 .V2H2O bng phoTig php sc k lng nh phn nh lng, s dng dung dch acid hydrocloric 0,01 M (TT) chun b dung dch chun gc codein phosphat v pha dung dch chun. iu chnh nng nu cn bng dung dch acid hydrocloric 0,01 M (TT).Yu cu: Khng c t hn 75 % ng paracetamol, C8H9NO2, v codein phosphat hemihydrat, C|8H2iN03.H3P04./2H20, so vi lng ghi n nhn c ha tan trong 30 pht.

nh lngTin hnh phng php sc k lng (Ph lc 5.3). Dung dch m: Ha tan 2,04 g kali dihydrophosphat (TT) trong khong 950 m\ nc. Thm 2 ml tre- thylamin (TT), ieu chnh v pH 2,35 bng acid phosphoric (TT), pha long vi nc thnh 000 ml v trn u.Pha ng: ^ Dung dch m - methanol (TT) (92 : 8 ). Lc v ui kh. iu chnh t l nu cn.Dung dch chun gc coden phosphat: Chun b dung dch codein phosphat chun trong pha ng c nng chnh xc khong 0,3 mg/m.Dung dch chun: Chuyn 30 mg, cn chnh xc, paracetamol chun v 1 0 0 / ml dung dch chun gc codein phosphat, J l t l lng ghi trn nhn (mg) ca codein phosphat hemihydrat v lng ghi trn nhn ca paracetamol (mg) trong mt vin, vo bnh nh mc 100 ml. Pha long bng pha ng n nh mc.Dung dch th: Cn 20 vin, tnh khi lng trung bnh vin, nghin thnh bt mn. Cn chnh xc mt lng bt vin tng ng vi khong 300 mg paracetamol vo bnh nh mc 1 0 0 m, thm khong 75 ml pha ng, siu m trong 10 pht. Pha long bng pha ng n vch v trn u. Ly chnh xc5 ml ung dch ny cho vo bnh nh mc 50 ml. Pha long bng pha ng n vch v trn u.iu kin sc k:Ct thp khng g (25 cm X 4,6 mm) c nhi pha tnh c (5 fim).Detector quang ph t ngoi t bc sng 214 nm. Tc dng: 1,5 ml/min.Th tch tim: 30 )J,1.Cch tin hnh:Kim tra tnh thch hp ca h thng sc k: Tin hnh sc k vi dung dch chun. phn gii gia

pic paracetamo v pic codein phosphat khng c nh hn 2,0; lch chun tung i ca cc din tch pic p ng t cc ln tim lp li khng c lm hn 2,0 % i vi pic paracetamol v 3,0 % i vi pic codein phosphat.Tin hnh sc k ln lt vi dung dch chun v dung dch th. Tnh hm lng paracetamol CgHNOa, v hm lng codein phosphat hemihydrat, C18H21NO3.H3PO4.V2H2O, c trong vin da vo din tch pic thu c t dung dch th, dung dch chun v hm lng C8H9NO2 ca paracetamol chun, hm lng Ci8H2iN0 3 .H3P0 4 .'/2H2 0 ca codein phosphat chun.

ng u hm lng codein phosphatCh phm c lng codein phosphat di 60 mg trong mt vin th phi t yu cu v ng u hm lng i vi codein phosphat (Ph lc 11.2).Tin hnh phong php sc k lng (Ph lc 5.3).Pha ng, dung mi ha tan, dung dch chun: Nh m t trong mc nh lng.Dung dch th. Ly 1 vin nghin thnh bt mn ri chuyn vo bnh nh mc 100 ml, thm khong 75 ml pha ng, siu m trong 10 pht. Pha long bng pha ng n vch v lc u. Lc, pha long dch lc bng pha ng c nng codein phosphat tng oTig vi nng codein phosphat trong dung dch chun.iu kin sc k v cch tin hnh: Nh m t trong mc nh lng.Cn c vo din tch pic thu c t dung dch th v dung dch chun v da vo hm lng c 18H21NO3 .H3PO4 . '/2H2O ca codein phosphat chun, tnh hm lng codein phosphat hemihydrat CigH2iN0 3 .H3P0 4 . ' / 2 H2O c trong vin.

Bo qunTrong bao b kn, trnh nh sng nhit 15 c n30 c.

Loi thucGim au, h st.

Hm lng thng dng300 mg paracetamol, 60 mg codein phosphat;600 mg paracetamol, 60 mg codein phosphat;500 mg paracetamol, 30 mg codein phosphat;500 mg paracetamol, 15 mg codein phosphat.

PEPSINPepsinumPepsin l ch phm dng bt cha men tiu protein, ly t nim mc cn ti ca d dy ln, tru, b hoc cu, tc dng trong mi trng acid (pH t 1 n 5), phi c hot lc khng t hn 0,5 n v trong 1 mg, tnh theo ch phm lm kh.

ng vt ly bt pepsin phi p ng cc yu cu v n th tch cn thit iu chnh n pH 1 , 6 0,1 nusc khe ng vt ph hp s dng cho ngi v yu cn bng dung dch acid hydrodoric 1 M (TT).cu ca c quan c thm quyn, Z)wg c/jw; Chun b dung dch pepsin chunPhi ch ra phong php dng loi b s nhim cha 0,5 n v/ml trong dung dch acid hydro-cloricvims hay cc tc nhn gy nhim khc. long (TT). Trc khi pha long iu chnh n pH

X, 1,6 0,1 nu cn bng dung dch acid hydrocloricA l.n Coit J ' ' r l "!;. *i' Chi ph ong vng 15 pht trac kh. dng. Chun b

nht, ht m . T a n tro n g n c , th c t k h n g tan tro n g " ' 7^ T x i., s , , s L z s 7, sZ vethanol 96 % . ng B.Dung dch trong nc c th hi c l v'C phn XJxm dung dch acid hydrocloric long (TT) vo ccng acid nh. ng nghim nh sau:nh tnh B: 1,0 mlTrong ci s cho 30 mg fibrin xanh T), to hn dch Si v Sib! 0,5 mlvi 20 ml dung dch acidhydrocloric long (TT). Lc 2 . S2b.T v Tb! 0,25 ml _hn dch v r a g i y l c VI dung dch acid T h m d u n g d ch o i c h i u v o c c o n g n g h im nh hydroclorc long (TT) cho n khi dch lc khng > Q ^ - rmu. Chc thng giy lc v ra fibrin xanh qua lthng vo mt binh nn bng 20 ml dung dch acid, , , , ~ y r r Z J " r i u - S3 v Ssb! 1,0 mlhydrodoric long TT). Lc hn hp ny trc khi 7 ' -J ' IT- . I 1 T u '1 iT Ta Thm 0,75 ml dung dch th vo ng nghim T v Tb.

f ITim m v ^ l m g Z id ir ic lo J o ^ tic (TT) vo^ v > t \ c t^ 2 M c m g d c h a c id h y ^ o c lo r ic c ng Sbk v R Trn uhng (77) y iu chnh n pH 16 0 1 (dung d ch dung dch hemoglobin (TT)

- trong cch thy nhit 25 01 c. Khi nhit fib . y 1 " ! ! ^ 1 cn bng- thm o rnl g ch hem l^obm (rr) l f t vo ng Shim b /s , . , s L I s b v T ri i u . Ttm 1 ; 5,0 ml ^ ddr hemoglobin (TT) ln l i v cch

uP .!^ - nhau 30 g % vo ng nghim S,, S3 v T Trnmu v dung dch th phi c mu xanh. i u ngay sau mi ln ^Mt khi lng do lm kh ng 10, pht sau khi thm (iung //c/ hemoglobinKling c qu 5,0 % (Ph lc 9.6). (T7) dng phn ng bng cch tim 0,0 ml dung(0,500 g; phosphor pentoxyd;.. p sut khng qu dch acid tricoroacetic (TT) vo ng Si, S2, S3 v T0,7 kPa; 60 C; 4 h). mi ln cch nhau 30 giy. Trn u.

. . Lc cc ng nghim (th v trng) qua giy lc th chGii hn vi khun c ra trc hng dung dch acidTng s vi khun hiu kh sng li c; Khng c tricloroacetic 5 % (TT) sm l w c va lm kh. Bqu 1 0 khun lc/gam. 5 m dch lc u. Ly 3,0 ml mi dch .lc ring bit1,0 g ch phm khng c c Escherichia coli v 10 g vo ng nghim cha 20 ml wc. Trn u.ch phm khng c c Salmonella (Ph lc 13.6). (Giy lc thch hp l giy lc p ng cc php thnh lng sm: Lc 5 m dung dch acid tricloroacetic 5 % (TT)Hot lc ca pepsin c xc nh bng cch so snh Jlng peptid khng b ta hi dung dch acid th'Ca dcMc 275 11m (Ph lc ^tricloroactic (TT) v c nh lng bng cch s acid trcloroacetic 5 % (TT) khng lc lm mudng thuc th phosphomolihdotungstic (TT), gii trng, phi t hn 0,04).phng tiig pht t c cht l dung dch hemoglobin, Ton b qu trnh trn c gh Bng A.vi lng peptid gii phng t pepsin i chiu vi Thm vo mi ng nghim \, dung dch natricng c cht v cng iu kin. hyroxyd 20 % (TT) \ 1,0 ml thuc th phospho-Trnli lc v lm si bt cc dung dch th y tiling tnolyhdotungstic (TT) bt u t cc ng trng sau ldch chun trong qu trnh nh lng. cc ng th theo th t nh trn.Dung dch th: Chun b ngay trc khi ng mt Sau 15 pht o hp th (Ph lc 4.1) ca ung dchdung dch ch phm cha 0,5 n v/ml irong dung Si, S2, S3, Sib, 8 2 b, Ssb, T v Tb bc sng 540 nmdch acid hydrocloric long TT). Trc khi pha long dng dch lc ca ng B lm mu trng, ,

Hiu chnh hp th ca dch lc t ng Si, S2, S3 Xc nh hot lc ca ch phm dng hp th cabng cch ly hp th o c tr i hp th dung dch th (T - Tb) t ng cong chun v tnhdch lc Sib, S2b, Ssb theo th t. ton pha long.V ng cong chun gia hp th tnh v hot Bo qunlc dung dch i chiu dng. ng trong l kn, trnh nh sng v nhit t

2C n8C .

Bng A

ng n ;him

Si Sib S2 Sib S3 Ssb T Tb B

Dung dich acid hydroclorc long (TT) (ml) 0,5 , 0,5 0,25 0,25 0,25 0,25 1 , 0

Dung dch i chiu (ml) 0,5 0,5 0,75 0,75 1 , 0 1 , 0

Dung dch th (ml) 0,75 0,75

Dung dch acid tricloroacetc T) (ml) 1 0 , 0 1 0 , 0 1 0 , 0 1 0 , 0 1 0 , 0

Trn + + + + +

Trong each thy 25 ""c + + + + + + + +

Dung dch hemoglobin (TT) (ml) 5,0 5,0 5,0 5,0 5,0

Trn + + + + +

Dung dch hemoglobin ( T) {m\) 5,0 5,0 5,0 5,0

Trn + + + +

Trong cch thy 25 c 10 pht + + + + + + + + +

Dung dch acid icloroacetic (TT) (ml) 1 0 , 0 1 0 , 0 1 0 , 0 1 0 , 0

Trn + + + +

Lc + + + + + + + + +

PETHIDIN HYDROCLORID Pethidini hydrocloridum

\ / /

'N ,CH3

. HCI

C,5H2,N02.HC1

Pethidin hydroclorid l ethyl-l-methyl-4-phenyl-pipe- ridin-4-carboxyIat hydroclorid, phi cha tr 99,0 % n 1 0 1 , 0 % C15H21NO2 .HCI, tnh theo ch phm lm kh.Sn xut: Nu ch phm d nh dng sn xut thuc tim th qui trnh sn xut phi c thm nh

chng minh gii hn tp cht B khng qu 0,1 phn triu.

Tnh chtBt kt tinh trng.Rt d tan trong nc, d tan trong ethanol 96 %, thc t khng tan trong ether.

nh tnhC th chn mt trong hai nhm nh tth sau:

p.t.l: 283,8 Nhm I;B, D.Nhm II: A, c, D.A. im chy ca ch phm phi tr 187 c n 190 c (Ph lc 6.7).B. Ph hng ngoi (Ph lc 4.2) ea ch phm phi ph hp vi ph hng ngoi ca pethidin hydrocloridchun.

c . Ha tan 0,1 g ch phm trong 10 ml ethanol (TT) v thm 10 m dung dch acid picric 1 % (TT). Ta tinh th thu c sau khi ra vi nc v sy kh 1 0 0 c n 105 c chy trong khong 186 c n 193 c. Trn u ng lng ta thu c v ch phm, xc nh im chy ca hn hp. im chy ca hn hp phi thp hn im chy ca ta t nht l 20 C (Ph lc 6.7).D. Thm 5 ml nc vo 5 ml dung dch s. Dung dch ny cho phn ng A ca ion clorid (Ph lc 8.1).

trong v mu sc ca dung dch Dung dch S: Ha tan 0,5 g ch phm trong nc khng c carbon dioxyd (TT) v pha long thnh25 ml vi cng dung mi.Dung dch s phi trong (Ph lc 9.2) v khng mu (Ph lc 9.3, phng php 2).

Gii hn acid - kimThm 0,2 ml dimg dch methyl (TT) v 0,2 ml dung dch natri hydroxyd 0,01 M (C) vo 10 ml dung dch s. Dung dch ny mu vng. Thm 0,3 ml dung dch acid hydrocloric 0,01 M (C), dung dch chuyn sang .

Tp cht BKhng c qu 10 phn triu i vi ch phm khng dng pha tim.Xc nh bng phng php sc k lng (Ph lc 5.3). Dung dch th (1): Ha tan 0,100 g ch phm trong hn hp acetonitril - nc ( 2 0 : 80) v pha long thnh 25,0 m! vi cng hn hp dung mi.Dung dch th (2)-. Ha tan 0,125 g ch phm trong hn hp gm 20 th tch acetonitri (TT) v 80 th tch nc v pha long thnh 1 0 , 0 ml vi cng hn hp dung mi.Dung dch i chiu (]): Pha long 0,5 ml dung dch th ( 1 ) thnh 1 0 0 , 0 ml bng hn hp acetonitril - nc ( 2 0 : 80).Dung dch i chiu (2): Ha tan 10,0 mg tp cht A ( -methyl-4-phenylpiperidin) ong hn hp acetonitri - nc ( 2 0 : 80) v pha long thnh 1 0 0 , 0 ml vi cng hn hp dung mi.Dung dch i chiu (3): Ha tan 12,5 mg tp cht B (l-methyl-4-phenyl-l,2,3,6 tetrahydropyridin) trong hn hp acetonitril - nc ( 2 0 : 80) v pha long thnh 10,0 ml vi cng hn hp dung mi. Pha long1.0 ml dung dch thu c thnh 100,0 ml bng hn hp acetonitril - nc ( 2 0 : 80).Dung dch i chiu (4): Pha long 5,0 ml dung dch i chiu (2 ) v 1 , 0 ml dung dch i chiu (3 ) thnh100.0 ml bng hn hp acetonitril - nc (20 : 80). Pha ng A. Hn hfp ng th tch dung dch natri peclorat 4,2 % v dung dch acid phosphoric 1,16 %, iu chnh pH ti 2,0 bng triethylamin (TT).Pha ng B: Acetonitri (TT).

iu kin sc k:Ct thp khng g (0,25 m X 4,0 mm) c nhi spherical end-capped octadecylslyl slica ge dng cho sc k (5 um) vi din tch b mt 340 mVg, kch thc l 10 nm v cha 19 % carbon.Tc dng: 1,0 ml/min.Detector quang ph t ngoi t bc sng 210 nm. Th tch tim: 50 (il Cch tin hnh:Tin hnh chy sc k theo chng trnh ghi bng sau:

Thi gian (min)

Pha ng A(% tt/tt)

Pha ng B(% tt/tt)

0 -15 80-75 20- 2515-31 7 5 - 5 5 25 - 4531-40 55 4540-41 55-80 4 5 - 2 041-50 80 2 0

Tim dung dch th (2) v dung dch i chiu (4). Thi gian lu tng i so vi pethidin (khong 24 pht) ca tp cht B khong 0,66, tp cht A khong 0,68 .Php th ch c gi tr khi trn sc k ca dung dch i chiu (4):T l tn hiu - nhiu; Ti thiu 10 ch pic u tin.T l nh - -hm: Ti thiu l 4 trong Hp = chiu cao ca pic tp cht B v Ho = chiu cao ca im thp nht trn ng cong tch pic ny t tp cht A. Trn sc k ca dung dch th (2) din tch pic tng ng vi tp cht B khng c ln hii din tch pic tong ng trong dung dch i chiu (4).

Tp cht lin quanXc nh bng phong php sc k lng (Ph lc 5.3). Tin hnh nh trong phn th tp cht B vi nhng thay i:Tim 20 (il dung dch th (1) v dung dch i chiu

Trn sc k ca dung dch i (1), din tch pic ca bt k tp cht no , khng c ln hn din tch pic chnh n sc k ca dung dch i chiu (1) (0,5 %). Tng din tch pic ca cc tp cht khng c ln hn 2 ln din tch pic chnh trn sc k ca dung dch i chiu ( 1 ) ( 1 , 0 %).B qua cc pic c din tch nh hn 0,1 ln din tch pic chnh trn sc k ca dung dch i chiu ( 1 ) (0,05%).

M t khi lng do lm khKhng c qu 0,5 % (Ph lc 9.6).(1,000 g; 100 c n 105 C).

Tro SulfatKhng c q 0,1 % (Ph lc 9.9, phng php 2). Dng 1,0 g ch phm.

nh lngHoa tan 0,220 g ch phm trong 50 ml ethanol (TT), thm 5,0 ml dung dch acid hydrocloric 0,01 N (TT). Chun bng dung dch natri hydroxyd 0,1 N (C). Xc nh im kt thc bn phng php chun o th ( Ph lc 10.2). c the tch gia 2 im.1 ml dung dch natri hydroxyd 0,1 N (C) tng ng vi 28,38 mg C 15H21NO2 .HCI.

Bo qunng trong ng kn, trnh nh sng.

Loi thucThuc gim au.

PHENOBARBITALPhenobarbitalum

p.t.l: 232,2

Phenobarbital l aci 5-ethyl-5-phenylbarbituric, phi cha t 99,0 % n 101,0 % Ci2Hi2N2 0 3 _tnh theo ch phm lm kh.

Tnh chtTinh th khng mu hay bt kt tinh trng, khng mi.Rt kh tan trong nc, hi tan ong cloroorm, tan trong ether, d tan trong ethanol 96 %. To thnh hp cht tan trong nc vi hydroxyd, carbonat kim v vi amoniac.

nh tnhC th chn mt trong hai nhm nh tnh sau:Nhm I: A, B. Nhm II: B, c , D.A. Xc nh im chy (Ph lc 6.7) ca ch phm v ca hn hp ng lng ch phm vi phenobarbital chun. im chy ca ch phm v ca hn hp phi khong 176 c. S khc bit v im chy ca 2 mu trn khng c qu 2 c .B. Ph hng ngoi (Ph lc 4.2) ca ch phm phi ph hp vi ph hng ngoi ca phenobarbital chun, c. Phng php sc k lp mng (Ph lc 5.4),Bn mng: Silica ge GF254.Dung mi khai trin: L lp di ca hn hp gm amonac m c - ethano 96%- cloroorm (5 : 15 : 80). Dung dch th: Ha tan 0,1 g ch phm trong ethanol 96 % (TT) v pha long thnh 100 ml vi cng dung mi.

Dung dch i chiu: Ha tan 0,1 g phenobarbital chun trong ethanol 96 % (TT) pha long thnh 100 ml vi cng dung mi.Cch tin hnh: Chm ring bit ln bn mng 10 |il mi dung dch trn. Trin khai sc k ti khi ung mi i c khong 18 cm. Quan st ngay bn mng di nh sng t ngoi bc sng 254 nm. Vt chnh ca sc k thu c t dung dch th phi ging v v tr v kch thc vi vt chnh ca sc k thu c t dung dch i chiu.D. Phn ng c trng ca barbiturat c hydro nhm NH khng b thay th (Ph lc 8.1).

trong v mu sc ca dung dchHa tan 1,0 g ch phm trong hn hp gm 4 ml dung dch natri hydroxyd 2 M ( TT) v 6 ml nc. Dung dch phi trong (Ph lc 9.2) v mu khng c m hn mu mu V (Ph lc 9.3 phng php 2).

Gii hn acidun si 1,0 g ch phm vi 50 ml nc trong 2 pht, ngui ri lc. Thm 0,15 m\ dung dch methyl (TT) vo 10,0 ml dch lc, dung dch c mu vng cam. chuyn sang mu vng, th tch dung dch natri hydroxyd 0,1 N (C) s dng khng c qu 0 , 1 ml.

Tp cht lin quanKhng c qu 0,5 %.Xc nh bng phng php sc k lp mng (Ph lc5.4).Bn mng: Silica gel GF254.Dung mi khai trin: L lp di ca hn hp amoniac m c - ethanol 9 6%- cloroform ( 5 :15: 80).Dung dch th: Ha tan 1,0 g ch phm trong ethano 96 % (TT) v pha long thnh 100 ml vi cng dung mi.Dung dch i chiu: Pha long 0,5 ml dung ch th thnh 100 ml bng ethanol 96 % (TT).Cch tin hnh: Chm ring bit ln bn mng 20 |J,1 mi dung dch trn. Trin khai sc k ti khi dung mi i c khong 15 cm. Quan st ngay bn mng di nh sng t ngoi bc sng 254 nm, phun thuc th diphenylcarbazon thy ngn (TT). kh bn mng ngoi khng kh, phun dung dch kali hydroxyd trong ethanol (TT) va mi pha. sy bn mng 100 c n 105 c trong 5 pht, quan st ngay tc khc. Khi quan st di nh sng t ngoi v sau khi phun thuc th, bt c vt ph no trn sc k thu c t dun dch th khng c m mu hn vt trn sc k o thu c t dung dch i chiu.

M t khi lng do lm khKhng c qu 0,5 % (Ph lc 9.6).(1,000 g; 100 C n 105 C; 2 h).

Tro sulfatKhng c qu 0,1 % (Ph lc 9.9, phong php 2). ng 1,0 g ch phm.

nh lngHa tan 0,100 g ch phm trong 5 ml pyrdin (TT), thm 0,5 ml dung dch thymolphtalein (TT) v 10 ml dm g dch bc nitrat 8,5 % trong pyridn (TT). Chun bng dung dch natri hydroxyd 0,1 N trong ethanol (C) n khi c mu xanh lam hon ton. Song song lm mu trng.1 ml dung dch n a tri hydroxyd 0,1 N trong ethanol (C) i\xng ng vi 11,61 mg C12H12N2O3.

BoqunTrong chai l kn.

Loai thucAn thn, chng co git.

Ch phmCn thuc, vin nn.

VIN NN PHENOBARBITAL Tabellae Phenobarbitali Vin nn Gardenal, Luminal

L vin nn cha phnobarbital.Ch phm phi p ng cc yu cu trong chuyn lun Thuc vin nn (Ph lc 1.20) v cc yu cu sau y;

Hm lirng phnobarbital, C12H 12N 2O 3, t 90,0 % n 110 ,0 % so vi lng ghi trn nhn.

Tnh chtVin mu trng.

nh tnhA. Ly mt lng bt vin tofng ng khong 60 mg phnobarbital lc vi 50 ml cloroform (TT) v lc. Bc hi dch lc n kh ri sy kh 105 c trong 2 gi. Ph hn ngoi (Ph lc 4.2) ca cn phi ph hp vi ph hng ngoi ca phnobarbital chun.B. Trong phn nh lng, thi gian lu ca pic chnh trn sc k ca dung ch th phi tng n vi thi gian luu ca pic phnobarbital trn sc k o ca dung dch chun.

ha tanThit b: Kiu cnh khuy.Mi trng ha tan: 900 ml nc.Tc quay. 50 r/min.Thi gian: 45 min.Cch tin hnh. Ly mt phn dung dch sau khi ha tan, lc, b 20 ml ch lc u. Pha long dch lc n nng thch hp bng m borat pH 9,6 (TT). o hp th (Ph lc 4.1) ca dung dch thu c bc sn cc i khong 240 nm. So snh vi dung dch chun c nng phnobarbital tng ng dung dch th pha trong cng dung mi. Tnh hm lng phnobarbital ha tan da vo cc hp th o c v nng phnobarbital trong dung dch chun.

Yu cu: Khng c t hn 75 % lng phenobarbital so vi lng ghi trn nhn c ha tan trong 45 pht.

nh lngTin hnh bng phong php sc k lng (Ph lc5.3).Dung dch m pH 4,5: Ha tan 6 , 6 g naM acetat (TT) v 3,0 ml acid acetic bng (TT) trong 1000 ml nc, iu chnh n pH 4,5 0,1 bng atid acetic bng (TT).Pha ng: Dung dch m pH 4,5 - methanol (3 : 2). Dung dch chun ni: Ha tan cafein chun trong hn hp ng th tch methanol (TT) v dung dch m pH 4,5 c n n g cafein khong 1 2 5 j.g/m l.Dung deh chun: Ha tan mt lng chnh xc khong 20,0 mg phenobarbital chun trong 15,0 ml dung dch chun ni, lc siu m nu cn, lc.Dung dch th: Cn 20 vin, tnh khi lng trung bnh vin v nghin thnh bt mn. Cn chnh xc mt lng bt vin tong ng vi khong 2 0 mg phenobarbital, thm 15,0 ml dung dch chun ni, lc siu m trong 15 pht, lc.iu kin sc k: Ct thp khng g (25 cm X 4 mm) c nhi pha tnh c (3 pm h 10 |Lun).Detector quang ph t ngoi t bc sng 254 nm. Tc dng: 2,0 ml/min.Th tch tim: 10 |J,1.Cch tin hnh:Kim tra kh nng thch hp ca h thng sc k: Tin hnh sc k vi dung dch chun, phn gii gia pic phenobarbital v cht chun ni khng c nh hn 1 ,2 ; h s i xng ca pic phenobarbital v pic chun ni khng c ln hon 2,0. lch chun tng i ca cc din tch pic p ng t cc ln tim lp li khng c qu 2,0 %. Thi gian lu tng i ca cafein khong 0 , 6 v ca phenobarbital l 1,0. C th iu chinh t l pha ng t iu kin trn.Tin hnh sc k ln lt vi dung dch chun v dung dch th.Tnh hm lng phenobarbital, C12H12N2O3, trong vin da vo din tch pic trn sc k ca dung dch chun, dung dch th v hm lng C12H12N2O3 trong phenobarbital chun.

Bo qunTrong ng kn, trnh nh sng.

Loi thucChng co git v an thn, gy ng.

Hm lng thng dng10 mg, 50 mg, 100 mg.

PHENOLPhenolum

CHO p.t.l; 94,1

Phenoi phi cha t 99,0 % n 100,5 % CeHgO.

Tnh chtTinh th hoc khi kt tinh khng mu hay mu hng nht hoc vng nht, c mi c trng, d chy ng. Tan trong nc, rt tan trong dicloromethan, ethanol 96 % v glycerin.

nh tnhA. Ha tan 0,5 g ch phm trong 2 ml dung dch amoniac 13,5 M (TT), phi tan hon ton. Pha long vi nc thnh 100 ml. Ly 2 ml dung dch ny, thm 0,05 ml dung dch natri hypoclort (3 % Cl) (TT) xut hin mu xanh v mu ny m dn.B. Ly 1 ml dung dch s, thm 10 ml nc v 0,1 m dung dch st (III) corid 10,5 % (TT), xut hin mu tm v mu ny mt i khi thm 5 ml propan-2-ol (TT).^c . Ly 1 ml dung dch s, thm 10 ml nc v 1 ml nc brom (TT) s c ta mu vng nht.

trong v mu sc ca dung dchDung dch S: Ha tan 1,0 g ch phm trong nc v pha long thnh 15 ml bng cng dung mi.Dung dch s phi trong (Ph lc 9.2) v khng c c mu m hn mu mu Ne (Ph lc 9.3, phng php 2 ).

Gii hn acidThm 0,05 ml dung dch da cam methyl (TT) vo 2 ml dung dch s. Dung dch phi c mu vng.

im ng cKhng c di 39,5 c (Ph lc 6 .6 ).

Cn sau khi bay hiKhng c qu 0,05 %.Ly 5,000 g ch phm lm bay hi n kh trn cch thy v sy 100 c n 105 c trong 1 gi.

nh lngHa tan 2,000 g ch phm trong nc v pha long thnh 1000,0 ml bng cng dung mi. Chuyn 25,0 ml dung dch ny vo 1 bnh thy tinh c nt mi. Thm50,0 ml dung dch brom 0,1 N (C) v 5 ml acid hydroclorc T). bnh v 30 pht (thnh thong lc), sau yn 15 pht na. Thm 5 m! dung dch kai iodid 20 % (TT), lc v chun bng dung dch natri thiosuat 0,1 N (C) cho n mu

vng nht. Thm 0,5 ml dung dch h tinh bt (TT) v10 ml cloro/orm (TT), tip tc va chun va lc mnh.Song song lm mu trng.1 m dung dch brom 0,1 N (C) tng ng vi1,569 mgCHeO.

Bo qunTrong l kn, nh nh sng.

Loi thucSt trng, bo qun chng nhim khun, chng nga.

PHENOXYMETHYLPENICILINPhenoxymethylpenicillnum

CifiHisNjOjS p.t.l:350,4

Phenoxymethylpetiicilin l acid {2S,5R,(>R)-3,3 -dime- thyl-7-oxo-6-[(phenoxyacetyl)amino]-4-thia-1 -azabicy- clo[3.2.0]heptan-2-carboxyic, c sn xut bng cch nui cy chng Penicilum notatum hoc cc chng cng h trong mi trng c cha tin cht thch hp, hay bng cc phng php khc. Tng hm lng ca phenoxymethylpenicilin v 4-hydroxv- phenoxymethylpeniciln phi t 95,0 % n 100,5 %, tnh theo ch phm khan.

Tnh chtBt kt tinh mu trng hoc gn nh trng, hi ht m. Rt kh tan trong nc, tan frong ethanol 96 %.

nh tnhC th chn mt trong hai nhm nh tnh sau:Nhm I: A.N hm II: B, c , D.A. Ph hng ngoai (Ph lc 4.2) ca ch phm phi ph hp vi ph hng ngoi ca phenoxymethy- penicilin chun.B. Ch phm phi t ch tiu pH.c . Tin hnh sc k lp mng theo nh tnh cc penicilin (Ph lc 8.2).D. Phn ng B trong php th phn ng mu ca cc penicilin v cephalosporin (Ph lc 8.3).

pHT 2,4 n 4,0 (Ph lc 6.2)Lc 50 mg ch phm trong 10 ml nc khng c carbon dioxyd (TT) to thnh hn dch.

Gc quay cc ringT +186 n +200 tnh theo ch phm khan (Ph lc 6.4).Ha tan 0,250 g ch phm trong butanol (TT) v pha long thnh 25,0 ml vi cng dung mi.

Tp cht lin quan Khng c qu 1,0 %.Xc nh bng phng php sc k lng (Ph lc 5.3) iu kin sc k, dung mi pha mu v cc dung dch i chiu: Ging nh phn nh Tig.Dung dch th: Chun b ngay trc khi dng. Ha tan 80,0 mg ch phm trong dung mi pha mu v pha long thnh 2 0 , 0 m! vi cng dung mi.Tim dung dch i chiu (4), tin hnh sc k ng dng vi thnh phn pha ng ging nh phn nh lng cho n khi pic ca phenoxymethylpenicilin c ra gii ra khi ct. iu chnh nhy ca h thng thu c t l tn hiu/ nhiu t nht bng3. Tim dung dch i chiu (5). Tim dung dch th, t chng trnh pha ng sao cho ban u ra gii vi pha ng ng dng ging nh trn. Sau khi phenoxymethylpenicilin c ra gii ra khi ct, ngay lp tc thay i t l pha ng theo chng trnh sau:

Thi gian(min)

Pha ng A (%) (tt/tt)

Pha ngB (%) (tt/tt) Ghi ch

0 - 2 0 6 0 -^ 0 4 0 ^ 1 0 0 Gradient tuyn tnh20-35 0 1 0 0 ng dng

35-50 0 -^ 6 0 100-^40 Cn bng ct

Tim dung mi pha mu, tin hnh sc k ging nh vi dung dch th thu c sc k mu trng. Trn sc k ca dung dch th, din tch ca bt k pic ph no, tr cc pic tng ng vi mu trng v pic ca 4-hydroxyphenoxymethylpen icil in, khng c ln hn din tch pc chnh ca dung dch i chiu (5).

4-HydroxyphenoxymethylpenicilinKhng c qu 4,0 %, tnh theo ch phm khan.Xc nh bng phng php sc k lng hiu nng cao (Ph lc 5.3) phn nh lng.

NcKhng c qu 0,5 % (Ph c 10.3).Dng 1,000 g ch phm.

nh lngPhng php sc k lng (Ph lc 5.3).Dung dch m acetat pH 3,5: Ha tan 25 g amon acetat (TT) t r o n g 2 5 m l nc, th m 3 8 m l dung dch acid hydrodoric 7 M (TT). iu chnh pH n 3,5 bng dung dch acid hydroclorc 2 M (TT) hoc dung dch amoniac 6 M (TT).

Pha ng A: Dung dch m acetat pH 3,5 - methanol - nc ( 1 0 : 30 ; 60).Pha ng B: Dung dch m acetat pH 2,5 - nc - methano{\0 : 35 : 55).Dung mi pha mu: Thm 500 ml nc vo 250 ml dung dch kali dihydrophosphat 0,2 M (TT), lc u. iu chnh pH n 6,5 bng dung dch natri hydroxyd 0,84 % (TT) v pha ong thnh 1000 ml vi nc. Dung dch th: Ha tan 50,0 mg ch phm trong dung mi pha mu v pha long thnh 50,0 ml vi cng dung mi.Dung dch i chiu (]): Ha tan 55,0 mg phenoxy- methylpenicilin kali chun trong dung mi pha mu v pha long thnh 50,0 ml vi cng dung mi.Dung dch i chiu (2): Ha tan 4,0 mg 4-hydroxy- phenoxymethylpenicilin chun trong dung mi pha mu v pha long thnh 1 0 , 0 ml vi cng dung mi. Pha long 5,0 ml dung dch thu c thnh 100,0 ml vi dung mi pha mu.Dung dch i chiu (3): Ha tan 10 mg phenoxy- methylpenicilin kali chun v 1 0 mg benzylpenicilin natri chun trong dung mi pha mu v pha long thnh 50 ml vi cng dung mi.Dung dch i chiu (4): Pha long 1,0 ml dung dch i chiu (1) thnh 20 ml vi dung mi pha mu. Pha long 1,0 ml dung dch thu c thnh 50 ml vi dung mi pha mu.Dung dch i chiu (5): Pha long 1,0 ml dung dch i chiu (1) thnh 25,0 ml vi dung mi pha mu.iu kin sc k:C t th p k h n g g (2 5 c X 4 ,6 m m ) c n h i p h a

tnh c (5 )am).Detector quang ph t ngoi t ti bc sng 254 nm. Tc dng: 1,0 ml/min.Th tch tim: 20 |J,1.Cch tin hnh: Cn bng ct vi pha ng l hn hp pha ng A v pha ng B (60 : 40). Tim dung dch i chiu (3). Php th ch c gi tr khi phn gii gia hai pic chnh t nht phi bng 6 , 0 (iu chnh t l gia pha ng A v pha ng B nu cn thit) v t s phn b khi lung (Dm) ca pic th hai (phenoxymethylpenicilin) phi t 5,0 n 7,0. Tim ring bit dung dch i chiu ( 1 ) su ln, lch chun tng i ca din tch pic khng c ln hn 1,0 %.Tim dung dch th, dung dch i chiu (1) v dung dch i chiu (2 ).Tnh hm lng phenoxymethylpenicilin v 4-hydroxy- phenoxymethyIpenici 1 in da vo din tch pic p ng. Nng phenoxymethyipenicilin ong dung dch chun bng nng phenoxymethylpenicilin kali nhn vi 0,902.

Bo qunBao b kn.

Loi thuc Khng sinh.

Ch phm Vin nn.

VIN NN PENICILIN V Tabellae Phenoxymethylpenicillin

L vin nn cha phenoxymethlpenicilin,Ch phm phi p ng cc yu cu trong chuyn lun Thuc vin nn (Phii lc 1.20) v cc yu cu sau:

Hm lng phenoxymethylpenicilin, C16H18N2O5S, t 90,0 % n 120,0 % so vi lng ghi trn nhn.

Tnh chtVin mu trng hoc trng ng, khng mi hoc c mi c bit ca penicilin.

nh tnhA. Lc k mt lcmg bt vin tng ng vi 80 mg phenoxymethylpenicilin vi 5 ml methanol (TT) trong bnh nh mc 250 ml, thm nc n nh mc, trn u, lc. Ph hp th nh sng (Ph lc 4.1) ca dch lc phi c cc cc i cc bc sng 268 nm v 274 nm, cc tiu bc sng 272 nm.B. Trong phn nh lng, thi gian lu ca pic chnh trn sc k ca dung dch th phi tng ng vi thi gian lu ca pic penicilin V trn sc k ca dung dch chun.

NcKhng c qu 3,0 % (Ph c 10.3).

ha tan (Ph lc 11.4).Thit b: Kiu cnh khuy.Mi trng ha tan: 900 ml nc.Tc quay: 50 r/min.Thi gian: A5 mn.Cch tin hnh: Ly mt phn dung dch mi trng sau khi ha tan, lc, b 20 ml dch lc u. Pha long vi mi trng ha tan c dung dch c nng thch hp (nu cn). o hp th (Ph lc 4.1) ca dch lc thu c cc i 268 nm, trong cc o dy1 cm, mu trng l mi trng ha tan. So snh vi dung dch phenoxymethylpenicilin kali chun c nng tng ng pha trong mi trng ha tan. Tnh lng phenoxymethylpenicilin, C16H18N2O5S, c ha tan ong vin da vo cc hp th o c v hm lng C16H18N2O5S ong phenoxymethylpenicilin kali chun.Yu cu: Khng c t hn 75 % lng phenoxy- methylpenGlin, C16H18N2O5S, so vi lng ghi trn nhn c ha tan trong 45 pht.

nh lngTin hnh bng phng php sc k lng (Ph lc 5.3) Pha ng: Nc - acetoniMl - acid acetic bng (650 : 350: 5,75).Dung dch phn gii: Dung dch c cha 2,5 mg benzylpenicilin kali v 2,5 mg phenoxymethylpenicilin kali trong 1 ml, pha trong pha ng.Dung dch chun: Dung dch phenoxymethylpenicilin kali chun c nng khong 2,5 mg/ml, pha trong pha ng.Dung dch th: Cn 20 vin, tnh khi lng trung bnh vin ri nghin thnh bt mn. Cn chnh xc mt lng bt vin tng ng khong 400 000 n v phenoxymethylpenicilin ha trong pha ng va 100,0 ml, lc k trong 5 pht, lc.iu kin sc k:C t th p k h n g g i ( 3 0 c m X 4 m m ), c n h i p h a

tnh c (3 |j.m n 10 am).Detector quang ph hp th t ngoi t bc sng 254 nm.Tc dng; 1,0 ml/min.Th tch tim: 10 X.Cch tin hnh:Tin hnh sc k vi dung dch phn gii, thi gian lu tng i ca pic benzylpenicilin khong 0 , 8 v ca pic phenoxymethylpenicilin l 1,0. Hiu nng ca ct xc nh trn pic phenoxymethylpenicilin khng c t hn 1800 a l thuyt, h s phn gii gia pic benzylpenicilin v pic phenoxymethylpenicilin khng c t hn 3,0.Tin hnh sc k vi dung dch chun, lch chun tng i ca din tch pic phenoxymethylpenicilin trn sc k thu c trong 6 ln tim lp li khng c ln hn 1,0 %. C th iu chnh t l pha ng t iu kin trn.Tin hnh sc k ln lt vi dung dch chun v dung dch th.Tnh hm lng phenoxymeiylpenicilin, C16H18N2O5S, trong vin da vo din tch pic trn sc k ca dung dch th, dung dch chun v hm lng C16H18N2O5S trong phenoxymethylpenicilin chun. Hot -lc l thuyt ca phnoxymethylpenicilin l 1695 IU trong 1 mg.Hot lc l thuyt ca phenoxymethylpenicilin kali l 1530 l trong 1 mg.

Bo qunTrnh m v nh sng, nhit khng qu 30 c.

Loi thucKhng sinh.

Hm lng thng dng200 000 cm v (IU); 400000 n v (IU).

P H E N O X Y M E T H Y L P E N I C L I N K A L I

Phenoxymehylpencllnum kalcum

C.^HnKNzOsS p.t.l: 388,5

Phenoxymethylpenicilin kali l mui kali ca acid (25',5i?,6i?)-3,3-dimethyl-7-oxo-6-[(phenoxyacetyl)- aiino]-4-thia-l-azabicyc!o[3.2.0]heptan-2-carboxylic, c sn xut bng cch nui cy chng Penicillium notatum hoc cc chng cng h trong mi trng c cha tin cht thch hp, hay bng cc phng php khc. Tng hm lng ca phenoxymethylpenicilin kali v 4-hydroxyphenoxymethypeniciin kai phi t95,0 % n 100,5 %, tnh theo ch phm khan.

Tnh chtBt kt tinh mu trng hoc gn nh trng. D tan trong nc, thc t khng tan trong ethanol 96 %.

B n h t n hC th chn mt trong hai nhm nh tnh sau:Nhm I: A, D. Nhm II: B, c , D.A. Ph hng ngoi (Ph lc 4.2) ca ch phm phi ph hp vi ph hng ngoi ca phenoxymethyl- penicilin kali chun.B. Tin hnh sc k lp mng theo nh tnh cc penicilin (Ph lc 8.2).c . Phn ng B trong php th phn ng mu ca cc penicilin v cephalosporin (Ph lc 8.3).D. Ch phm cho phn ng (A) ca ion kali (Ph lc8.1)

T 5,5 n 7,5 (Ph lc 6.2)Ha tan 100 mg ch phm trong nc khng c carbon dioxyd (TT) v pha long thnh 20 ml vi cng dung mi.

Gc quay cc ringT +215 n +230 tnh theo ch phm khan (Ph lc 6.4).Ha tan 0,250 g ch phm trong nc khng c carbon dioxyd (TT) v pha long thnh 25,0 ml vi cng dung mi.

Tp cht lin quanKhng c qu 1,0 %.Xc nh bng phng php sc k lng (Ph lc 5.3)

iu kin sc_ k, dung mi pha mu v cc dung dch i chiu: Ging nh phn nh lng.Dung dch th: Chun b ngay trc khi dng. Ha tan 80,0 mg ch phm trong dung mi pha mu v pha long thnh 2 0 , 0 ml vi cng dung mi.Tim dung dch i chiu (4), tin hnh sc k ng dng vi thnh phn pha ng ging nh phn nh lng cho n khi pic ca phenoxymethylpenicilin c ra gii ra khi ct. iu chnh nhy ca h thng thu c t l tn hiu/ nhiu t nht bng 3. Tim dung dch i chiu (5). Tim dung dch th, t chng trnh pha ng sao cho ban u ra gii vi pha ng ng dng ging nh trn. Sau khi phenoxy- methylpenicilin c ra gii ra khi ct, ngay lp tc thay i t l pha ng theo chng trnh sau:

Thi gian(min)

Pha ng A(%) (tt/tt)

Pha ng B(%)(/) Ghi ch

0 - 2 0

20-3535-50

6 0 -> 0

0

0 ^ 6 0

4 0 ^ 1 0 0

1 0 0

lOQ 40

Gradient tuyn tnh ng dng Cn bng ct

Tim dung mi pha mu, tin hnh sc k ging nh vi dung dch th thu c sc k mu trng. Trn sc k ca dung dch th, din tch ca bt k pic ph no, tr cc pic chnh v pic ca 4-hydroxy- phenoxymethylpenicilin, khng c ln hn din tch pic chnh ca dung dch i chiu (5).

4-HydroxyphenoxymethylpeniciIin kaliKhng c qu 4,0 %, tnh theo ch phm khan.Xc nh bng phng php sc k lng (Phu lc 5.3) phn nh lng.

NcKhng c qu 1,0 % (Ph lc 10.3).Dngl,000 g ch phm.

nh lngPhng php sc k lng (Ph lc 5.3).Dung dch m acetat pH 3,5: Ha tan 25 g amoni acetat (TT) trong 25 ml nc, thm 38 ml dung dch acid hydrocoric 7 M (TT). \hx chnh pH n 3,5 bng dung dch acid hydrocloric 2 M (TT) hoc dung dch amoniac 6 M (TT).Pha ng A: Dung dch m acetatpH 3,5 - methanol - nc (10 ; 30 : 60).Pha ng B: Dung dch m acetat pH 3,5 - nc - methanol (10 : 35 : 55).Dung mi pha mu: Thm 500 ml nc vo 250 ml dung dch kali dihydrophosphat 0,2 M (TT), lc u. iu chnh pH n 6,5 bng dung dch natri hydroxyd 0,84 % (TT) v pha long thnh 1000 ml vi nc. Dung dch th: Ha tan 50,0 mg ch phm trong dung mi pha mu v pha long thnh 50,0 ml vi cng dung mi.

Dung dch i chiu (1):^ Ha tan 50,0 mg phenoxy- methylpenicilin kali chun trong dung mi pha mu v pha long thnh 50,0 ml vi cng dung mi.Dung dch i chiu (2): Ha tan 4,0 mg 4-hydroxy- phenoxymethylpenicilin chun trong dung mi pha mu v pha long thnh 10,0 ml vi cng dung mi. Pha long 5,0 ml dung dch thu c thnh 100,0 ml vi dung mi pha mu.Dung dch i chiu (3): Ha tan 10 mg phenoxy- methylpenicilin kali chun v 10 rag benzyl-penicilin natri chun trong dung mi pha mu v pha long thnh 50 ml vi cng dung mi.D m g dch i chiu (4): Pha long 1,0 ml dung dch i chiu (1) thnh 20 ml vi dung mi pha mu. Pha long 1,0 ml dung dch thu c thnh 50 ml vi dung mi pha mu.Dung dch i chiu (5): Pha long 1,0 ml dung dch i chiu (1) thnh 25,0 ml vi dung mi pha mu. iu kin sc k:C t th p k h n g g (2 5 c m X 4 ,6 m m ) c n h i p h a

tnh c (5 *Detector t ngoi t bc sng 254 nm.Tc dng: 1,0 ml/min.T h t c h t im ; 2 0 |Lil.

Cch tin hnh: Cn bng ct vi pha ng l hn hp pha ng A v pha ng B (60 : 40). Tim dung dch i chiu (3). Php th ch c gi tr khi phn gii gia hai pic chnh t nht phi bng 6,0 (iu chnh t l gia pha ng A v pha ng B nu cn thit) v t s phn b khi lng (Dm) ca pic th hai (phenoxymethylpenicilin) phi t 5,0 n 7,0. Tim ring bit dung dch i chiu (1) su ln, lch chun tng i ca din tch pic khng c ln hoTi 1,0 %.Tim dung dch th, dung dch i chiu (1) v dung dch i chiu (2).Tnh hm lng phenoxymethylpenicilin kali v 4- hydroxyphenoxymethyIpenici 1 in da vo din tch picp Tig.Hm lng 4-hydroxyphenoxymethylpenicilin kali bng hm lng 4-hydroxyphenoxymethylpenicilin nhn vi h s hiu chnh c cung cp km theo cht i chiu.

Bo qunBao b kn.

Loi thucKhng sinh.

Ch phmVin nn, bt pha hn dch ung.

VIN NN PENICILIN V KALI Tabellae Phenoxmethylpenicillini Kalii

L vin nn cha phenoxymethylpenicilin kali.Ch phm phi p ng cc yu cu ong chuyn lun Thuc vin nn (Ph lc 1.20) v cc yu cu sau:

Hm lng phenoxymethylpenicilin, C16H18N2O5S, t 90,0 % n 120,0 % so vi lng ghi trn nhn.

Tnh chtVin mu trng hoc trng ng, khng mi hoc c mi c bit ca penicilin.

nh tnhA. Lc k mt lng bt vin tong ng vi khong 80 mg phenoxymethylpenicilin vi khong 200 ml nc ong bnh nh mc 250 ml, thm nc n nh mc, trn u, lc. Ph hp th (Ph lc 4.1) ca dch lc thu c phi c cc i cc bc sng 268 nm v 274 nm, cc tiu bc sng 272 nm.B. Trong phn nh lng, thi gian lu ca pic chnh trn sc k ca dung dch th phi tng ng vi thi gian lu ca pic phenoxymethylpenicilin trn sc k ca dung dch chun.c . t 0,5 g bt vin, ri nung n cn o mu trng. ngui, thm vo cn 5 ml dimg dch acid acetic 2 M (TT). un si, ngui, lc. Dch lc phi cho phn ng B ca ion kali (Ph lc 8.1).

Mt khi lng do lm khKhng c qu 1,5 % (Ph lc 9.6).(Dng 0,5 g bt vin nghin mn, sy 3 gi trong chn khng, 60 C).

ha tan (Ph lc 11.4)Thit b: Kiu cnh khuy.Mi ng ha tan: 900 ml m phosphat chun pH6,0 (TT).Tc quay: 50 r/min.Thi gian: 45 pht.Cch tin hnh: Ly mt phn dung dch mi Tig sau khi ha tan, lc, b 20 ml dch lc u. Pha long vi mi trng ha tan c dung dch c nng thch hp (nu cn). o hp th (Ph lc 4.1) ca dung dch cc i 268 nm, trong cc o dy 1 cm, m trng l mi trng ha tan. So snh vi dung dch phenoxymethylpenicilin kali chun c nng tng ng pha trong mi trTig ha tan. Tnh lng phenoxymethylpenicilin, Ci6HigN2 0 5 S, c ha tan ong vin da vo cc hp th o c v hm lng Ci6HigN2 0 5 S trong mu chun.Yu cu: Khng c t hn 75 % lng phenoxy- methylpenicilin, C 16H18N2O5S, so vi lng ghi trn nhn c ha tan trong 45 pht.

nh lngTin hnh bng phng php sc k lng (Ph lc 5.3). Pha ng: Nc - acetonitril - acid acetic bng (650 : 350 : 5,75).Dung dch phn gii: Dung dch c cha 2,5 mg benzyl- penicilin kali v 2,5 mg phenoxymeiylpenicilin kali trong 1 ml, pha trong pha ng.Dung dch chun: Dung dch phenoxymethylpenicilin kali chun c nng khong 2,5 mg/ml, pha trong pha ng.Dung dch th: Cn 20 vin, tnh khi lng trung bnh vin ri nghin thnh bt mn. Cn chnh xc mt lng bt vin tng ng khong 400 000 n v phenoxymethylpenicilin ha trong pha ng va 100,0 ml, lc k trong 5 pht, lc.iu kin sc k:C t th p k h n g g ( 3 0 c m X 4 m m ), c n h i p h a

tnh c (3 xm n 10Detector quang ph hp th t ngoi t bc sng 254 nm.Tc dng: 1,0 ml/min.T h t c h t i m : 1 0 |Lil.Cch tin hnh:Tin hnh sc k vi dung dch phn gii, thi gian lu tng i ca pic benzylpenicilin khong 0 , 8 v ca pic phenoxymethylpenicilin l 1,0. Hiu nng ca ct xc nh trn pic phenoxymethylpenicilin khng c t hon 1800 a l thuyt, h s phn gii gia pic benzylpenicilin v pic phenoxymethylpenicilin khng c t hn 3 ,0 .Tin hnh sc k vi dung dch chun, lch chun tng i ca din tch pic phenoxymethylpenicilin trn sc k thu c trong 6 ln tim lp li khng c ln hn 1,0 %. C th iu chnh t l pha ng t cc iu kin trn,Tin hnh sc k ln lt vi dung dch chun v dung dch th.Tnh hm lng phenoxymethylpenicilin, C16H18N2O5S, trong vin da vo din tch pic trn sc k ca dung dch th, dung dch chun v hm lng C16H18N2O5S trong phenoxymethylpenicilin kali chun. Hot lc l thuyt ca phenoxymethylpenicilin l 1695 l trong 1 jmg.Hot lc l thuyt ca phenoxymethylpenicilin kali l 1530 l trong 1 mg.

Bo qunTrnh m v nh sng, nhit khng qu 30 c.

Loi thucKhang sinh.

Hm lng thng dng200 000'n v (IU); 400 000 n v (IU).

PHENYLPROPANOLAMIN HYDROCLORID Phenylpropanolamini hydrochloridum

v ng phn i quang

CHnNO.HCl p.tl: 187,7

Phenylpropanolamin hydroclorid l (li?S',25'i?)-2-amino-1 -phenyIpropan-1 -ol hydroclorid, phi cha t 99,0 % n 101,5 % C9 H 1 3NO.HCI, tnh theo ch phm lm kh.

Tnh chtBt kt tinh trng hay gn nh trng. D tan trong nc v ethanol 96 %, thc t khng tan t-ong dicloromethan.

nh tnhC th chn mt trong hai nhm nh tnh sau:Nhm I; , E. 'Nhm II: B, c , D, E.A. Ph hng ngoi (Ph lc 4.2) ca ch phm phi ph hp vi ph hng ngoi ca phenylpropanolamin hydroclorid chun. Xc nh di dng a nn khng cn kt tinh li.B. im chy t 194 c n 197 c (Ph lc 6.7).c . Quan st sc k thu c php th Tp cht lin quan, v t chnh trn sc k ca dung dch th (2 ) phi ph hp v v tr, mu v kch thc vi vt chnh trn sc k ca dung dch i chiu ( 1 ).D. Ha tan 50 mg ch phm trong 5 ml nc, thm 0,2 ml dung ch ng suat 12,5 % (TT) v 0,3 ml dung dch natri hydroxyd long (TT), xut hin mu tm. Thm 2 ml ether (TT) v lc, c ta mu tm to thnh gia 2 lp dung dch.E. Ch phm phi cho phn ng A ca ion clorid (Ph lc 8 .1 ).

trong v mu sc ca dung dchDung dch S: Ha tan 1,25 g ch phm trong nc v pha long thnh 25 ml vi cng dung mi.Dung dch s phi trong (Ph lc 9.2) v khng mu (Ph lc 9.3, phng php 2).

Gii hn acid - kimThm 0,1 ml dung dch methyl (TT) v 0,2 m dung dch natri hydroxyd 0,01 N (C) vo 10 ml dung dch s, dung dch c mu vng. Thm 0,4 ml dung dch acd hydrocloric 0,01 N (C), dung dch c mu .

Tp cht lin quanPhong php sc k lp mng (Ph lc 5.4).

Bn mng: Silica gel H.Dung mi khai trin: Amoniac - ethanol 96 % - butanol ( 6 24 : 70).Dung dch th (1): Ha tan 0,20 g ch phm trong ethanol 96 % (TT) v pha long thnh 10 ml vi cng dung mi.Dung dch th (2): Pha long 1 ml dung dch th (1) thnh 10 ml bng ethanol 96 % (TT).Dung dch i chiu (1): Ha tan 20 mg phenylpro- panolamin hydroclorid chun trong ethanol 96 % (TT) v pha long thnh 1 0 ml vi cng dung mi.Dung dch i chiu (2): Pha long 1 ml dung dch i chiu (1) thnh 10 ml bng ethanol 96 % (TT).Dung dch i chiu (3): Ha tan 20 mg norpseu- doephedrin hydroclorid chun ong ethanol 96 % (TT), thm 1 ml dung dch th ( 1 ) v pha long thnh 1 0 ml bng ethanol 96 %.^Dung dch i chiu (4): Ha tan 60 mg amon clord (TT) trong methanol (TT) v pha long thnh 10 ml vi cng dung mi.Cch tin hnh: Tmc khi chm sc k, phun ln bn mng dung dch na tetraborat 2 % ( 8 ml cho bn mng kch thc 10 cm X 20 cm). kh bn mng di mt lung kh lnh trong 30 pht. Chm ring bit ln bn mng 1 0 fj.l mi dung dch trn thnh di c kch thc 10 mm X 3 rnm. Trin khai sc k n khi dung mi i c khong 1 0 cm. sy kh bn mng di mt lung kh m n khi dung mi bay C15H12N2O ht, ngui. Phun dung dch nnhydrn 0,2 % trong

________1 n _ ' ___ 1 .______ 1 1 n o r ^ A._________

nh lngHa tan 0,1500 g ch phm trong hn hp gm 5 ml dung dch acid hydrocloric 0,01 N (C) v 50 ml ethanol 96 % (TT), Chun bng duti dch natri hydroxyd 0,1 N (C). Xc nh iem ket thc bng phng php chun o in th (Ph lc 10.2). c th tch dung dch natri hydroxyd 0,1 N (C) thm vo gia hai im un.1 ml dung dch natr hydroxyd 0,1 N (C) toTig otig vi 18,77 mg CHnN.HCl.

Bo qunTrong bao b kn, trnh nh sng.

Loi thucThuc ging thn kinh giao cm.

Ch phmVin nn, nang phi hp.

PHENYTOINPhenytoinum

p.tl: 252,3

ethanol 96 % v sy bn mng 110 c trong 15 pht. Trn sc k ca dung dch th (1), bt k vt ph no, ngoi vt chnh v vt tong ng vi amoni clorid, khng c m hn vt thu c n sc k ca dung dch i chiu (2) (1,0 %). Php th ch c gi tr khi sc k ca dung dch i chiu (3) cho 2 vt tch r rt.

PhenylpropanolaminHa tan 1,0 g ch phm trong dung dch acid hydro- coric 0,01 N (C) v pha long thnh 50,0 ml vi cng dung mi. hp th nh sng (Ph lc 4.1) ca dung dch thu c bc sng 283 nm khng c ln hn 0 ,1 0 .

Kim loi nngKhng c qu 20 phn triu (Ph lc 9.4).Ly 12 ml dung dch s tin hnh theo phng php 1. Dng dung dch ch mu 1 phn triu (TT) chun b mu i chiu.

M t khi lng do lm khKhng c qu 0,5 % (Ph lc 9.6).(1,000 g, 100 c en 105 C).

Tro SulfatKhng c qu 0,1 % (Ph lc 9.9, phng php 2). Dng 1,0 g ch phm.

Phenytoin l 5,5-diphenylimidazolidin-2, 4-dion, phi cha t 99,0 % en 10 1 , 0 % C 15H 12N 2O2, tnh theo ch phm lm kh.

Tnh chtBt kt tinh trng hoc gn nh ng, khng mi hoc gn nh khng mi.Thc t khng tan trong nc, hi tan trong ethanol 96 %, kh tan trong cloroform v ether. Rt kh tan trong methylen clorid. Tan trong cc dung dch hydro- xyd kim long.nh tnhC th chn mt trong hai nhm nh tnh sau:Nhm I: A.Nhm II: B, c, D.A. Ph hng noi (Ph lc 4.2) ca ch phm phi ph hp vi pho hng ngoi ca phenytoin chun.B. Trong mc th Tp cht lin quan, vt chnh trong sc k thu c ca dung dch th (2 ) phi c v tr v kch thc ging vi vt chnh trong sc k thu c ca dung dch i chiu ( 1 ).c. Cho vo 10 mg ch phm 1 ml nc v 0,05 ml amoniac (TT). un n si, thm 0,05 ml dung dch ng suat 5 % trong dung dch amoniac 2 M (TT) v lc u. Ta kt tinh mu hng xut hin.D. Phi p ng cc yu cu ca php th Tro Sulfat.

trong v mu sc ca dung dch Dung dch ca 1,0 g ch phm trong hn hp gm 20 ml nc v 5 ml dung dch natri hydroxyd 1 M phi trong (Ph lc 9.2) v khng c c mu m hn mu ca mu mu VN (Ph lc 9.3, phng php 2).

Gii hn acid - kimThm 45 ml nc vo 1,0 g ch phm, un si khong2 pht, ngui v lc. Ra phu ic bng nc khng c carbon dioxyd (TT). Pha long dch lc v nc ra phu lc bng nc khng c carbon dioxyd (TT) thnh 50 ml. Ly 10 ml dung dch thu c v thm 0,15 ml dung dch methyl (TT), mu ca ch th phi chuyn sang mu khi thm khng qu 0,5 ml dung dch acid hydrodoric 0,01 M (C). Ly 1 0 ml dung dch thu c v thm 0,15 ml dung dch xanh bromothymol (TT), mu ca ch th phi chuyn sang mu xanh lam khi thm khng qu 0,5 ml dung dch natri hydroxyd 0,01 M (C).

Tp cht lin quanXc nh bng phng php sc k lp mng (Ph lc5.4). ^Bn mng'. Silca ge Gp2S4 (TT). Trc khi dng, ra bn mng bng hn hp gm 30 ml dioxan (TT) v 75 ml hexan (TT). bn mng kh ngoi khng kh. Dung mi khai trin: Dioxan - hexan (30 : 75).Dung mi ha tan mu\ Hn hp ng th tch ca aceton (TT) v methanol (TT) .Dung dch th (1): Ha tan 0,40 g ch phm trong dung mi ha tan mu v pha long thnh 1 0 ml vi cng dung mi.Dung dch th (2): Pha long 1 ml dung dch th (1) thnh 2 0 ml bng dung mi ha tan mu.Dung dch i chiu (1): Ha tan 20 mg phenytoin chun trong dung mi ha tan mu v pha long thnh 1 0 ml bng cng dung mi.Dung dch i chiu (2): Ha tan 8 mg benzophenon (TT) trong dung mi ha tan mu v pha long thnh 1 0 0 ml bng cng dung mi.Dung dch i chiu (3): Ha tan 8 mg benzil (TT) trong dung mi ha tan mu pha long thnh 1 0 0 ml bng cng dung mi.Dung dch i chiu (4): Pha long 1 ml dung dch th ( 1 ) thnh 100 ml bng dung mi ha tan mu. Dung dch i chiu (5): Trn u 1 ml dung dch i chiu (2) v 1 ml dung dch i chiu (3).Cch tin hnh: Chm ring bit ln bn mng 10 |U.1 mi dung dch trn, dng lung kh lnh lm kh bn mng trong khong 2 pht. Trin khai sc k n khi dung mi i c 15 cm. bn mng kh ngoi khng kh v quan st di nh sng t ngoi bc sng 254 nm. Trn sc k ca dung dch th (1) cc vt tng ng vi vt ca benzopheton v benzil khng c m mu hn vt thu c trn sc k ca dung dch i chiu (2) v (3) (0,2 %), cc vt ph

khc tr vt chnh v vt tng ng vi benzophenon v benzil khng c m mu hn vt thu c trn sc k ca dung dch i chiu (4) (1 %). Php th ch c gi khi sc k thu c ca dung dch i chiu (5) cho thy 2 vt tch r rng.

Kim loai nngKhng c q^ u 10 phn triu (Ph lc 9.4.8).Ly 2,0 g ch phm th theo phng php 3. Dng2 ml dun dch ch mu 10 phn triu (TT) chun b mu oi chiu.

Mt khi lng do lm khKhng c qu 0,5 % (Ph lc 9.6).(1,000 g; 100 Cn 105 C).Tro SulfatKhng c qu 0,1 % (Ph lc 9.9, phng php 2). Dng 1,0 g ch phm.

nh lngHa tan 0,200 g ch phm trong 50 ml dimethyl for- mamid (TT). Chun bn duu, dch natri methoxyd 0,1 M (C). Xc nh iem ket thc bng phong php chun o in th (Ph lc 10.2).1 ml dimg dch natri methoxyd 0,1 M (C) tng ng vi 25,23 mg C15H 12N2O2 .

Bo qunng trong bnh kn.

VIN NN PHENYTOIN Tabellae Phenytoini

L vin nn hay vin nn bao phim cha phenytoin natri.Ch phm phi p ng cc yu cu trong chuyn lun Thuc vin nn (Ph lc 1.20) v cc yu cu sau y:

H m l n g p h e n y t o in n a t r i , C i5 H i]N 2 N a 0 2 , t 90,0 % n 1 1 0 , 0 % so vi lng ghi trn nhn.

Tnh chtVin nn mu trng, hay vin bao mu ng nht. nh tnhA. Cn mt lrng bt vin tong ng vi khong 0,5 g phenytoin natri, thm 10 ml nc (TT), lc trong 10 pht, lc (dch lc A). Ly 2 ml dch lc A, thm vi git dun^ dch thy ngn (II) clord 5 % (TT), xut hin ta ang khng tn trong dung dch amonac 10%(TT).B. Ly 0,5 ml dch lc A, cho bay hi n kh. cn thu c cho phn ng ngn la ca ion natri (Ph lc8 -1 )- , , . , , c. Trong phn Tp cht lin quan, vt chnh trn sc k ca dung dch th (2 ) phi ph hp vi vt chnh trn sc k ca dung dch i chiu (3 ) v v tr, mu sc v kch thc.

Tp cht Hn quanTin hnh bng phong php sc k lp mng (Ph lc 5.4).Bn mng: Silica gel Gp254-Dung mi khai trin: Propcm-2-ol - doroform - amoniac /J ,5M (45 :45 : 10).^Dung dch th (ly. Lc k mt lng bt vin cha 0,2 g phenytoin natri vi 5 ml methanol (TT) lm m trn cch thy, lc v lc. S dng dch lc.Dung dch th (2): Pha long 1 ml dung dch th (1) thnh 10 ml vi methanol (FT).Dung dch i chiu (I): Pha long 1 ml dung dch th(2) thnh 20 ml vi methanol (TT).Dung dch i chiu (2): Dung dch benzophenon chun 0,020 % trong methanol (TT).Dung dch i chiu (3): Dung dch phenytoin natri chun 0,4 % trong methanol (TT).Cch tin hnh: Chm ring bit ln bn mng 10 |xl mi dung dch trn, lm kh cc vt bng lung khng kh lnh trong 2 pht. Trin khai sc k n khi dung mi i c 15 cm. Ly bn mng ra, sy kh 80 c trong 5 pht v quan st di nh sng t ngoi bc sng 254 nm. Trn sc k thu c ca dung dch th ( 1), bt k vt ph no tng ng vi benzo- phenon khng c m mu hn vt trn sc k thu c ca dung dch i chiu (2) (0,5 %) v bt k vt ph no khc khng c m mu hn vt trn sc k thu c ca dung dch i chiu ( 1 ) (0,5 %).

ha tan (Ph lc 11.4)Thit b: Kiu cnh khuy.Mi trng ha tan: 500 ml nc.Tc quay: 100 r/min.Thi gian: 45 min.Cch tin hnh. Ly mt phn dung dch mi trng ha tan mu th, lc, loi b 2 0 ml dch lc u. o hp th (Ph lc 4.1) ca dch lc bc sng 258 nm (Ph lc 4.1) trong cc o dy 1 cm, dng nc lm mu trng. So snh vi dung dch phenytoin natri chun c nng chnh xc khong 0 , 2 mg/ml. Tnh hm lng phenytoin natri, Ci5HiiN2Na0 2 , ha tan trong mi vin da vo hp th o c ca dung dch chun, dung dch th v nng Ci5HiiN2Na0 2 ca dung dch chun.Yu cu: Khng c t hn 75 % lng phenytoin natri so vi lng ghi n nhn c ha tan trong 45 pht.

nh lngCn 20 vin ( loi b lp v bao, nu l vin bao), t nh khi lTig trung bnh vin v nghin thnh bt mn. Cn chnh xc mt lng bt vin tong ng vi kVong 0,3 g phenytoin natri vo bnh gn, thm2 5 ml nc (TT), lc trong 10 pht. Thm 50 ml ether

(TT) v 10 git dung dch xanh bromophenol (TT). Chun bng dung dch acid hydrocloric 0,1 N (C), lc mnh, cho n khi lp nc c mu xm lam. Chuyn lp nc vo bnh nn nt mi, ra lp ether vi 5 ml nc. Gp dch ra vo lp nc trong bnh nn, thm 20 ml ether (TT), tip tc chun vi dung dch acid hydrocloric 0,1 N (C), lc mnh, cho n khi lp nc c mu lc nht.1 ml dung dch acid hydrocorc 0,1 N (C) tng ng vi 27,43 mg C15H1 iN2Na0 2 .

Bo qunNi kh mt, trnh nh sng.

Loi thucChng ng kinh.

Hm lng thng dng50 mg; 100 mg.

PHTHALYLSULFATHIAZOLPhthalylsulfathiazolum

CO2H 0

CH,3N305S2 p.t.1; 403,4

Phthalylsulfathiazol l acid 2-[[4-(thiazol-2-ylsulph- amoyl)phenyl]carbamoyl]benzoic, phi cha t 98,5 % n 101,5 % C17H13N3O5S2, tnh theo ch phm lm kh.

Tnh chtBt kt tinh trng hoc trng nh vng. Thc t khng tan ong nc, d tan trong dimethylformamid, kh tan trong aceton v ethanol 96 %.

nh tnhC th chon mt trong hai nhm nh tnh sau:Nhm I: A, B, E.Nhm II: B, c , D, E.A. Ph hng ngoi (Ph lc 4.2) ca ch phm phi ph hp vi ph hng ngoi ca phthalylsulfathiazol chun.B. Ly 1 g ch phm, thm 8,5 ml dm g dch natri hydroxyd 2 M (TT), un si hi lu trong 30 pht. ngui, thm 17,5 ml dung dch acid hydrocloric long (TT). Lc mnh v lc. Trung ha dch lc bng dung dch natr hydroxyd 2 M (TT). Lc, ra ta bng nc. Kt tinh li ta trong nc v sy kh tinh

th 100 c n 105 c. Nhit nng chy ca tinh th thu c t 200 c n 203 c (Ph lc

c . Ly 0,1 g ch phm cho vo mt ng nghim, thm3 ml dung dch acid sulfuric 1 M (TT) v 0,5 g bt km (TT). Kh c to thnh lm en giy tm ch (II) acetat (TT).D. Ly khong 0,1 g ch phm, thm 0,5 g resorcinol (TT) v 0,3 ml acid sulfuric (TT), un nng trn cch thy cho n khi hn hp ng nht. e ngui, thm 5 ml dung dch natri hydroxyd 2 M (TT), lc u, hn hfp c mu nu. Pha long 0,1 ml hn hp thu c thnh 25 ml vi nc. Dung dch c hunh quang xanh lc m, mt i khi acid ha dung dch.E. Ha tan khong 10 mg tinh th thu c t phn ng nh tnh B trong 200 ml dung dch acid hydro- cloric 0,1 M (TT). 2 ml dung dch thu c cho phn ng ca amin thm bc nht (Ph lc 8.1) vi kt ta mu cam.

trong v mu sc ca dung dchHa tan 1,0 g ch phm trong 20 ml dung dch nai hydroxyd 1 M (TT). Dung dch thu c phi trong (Ph lc 9.2) v c mu khqg c m hon dung dch mu mu VLs (Ph lc 9.3, phng php 2).G i i h n a c id

Ly 2,0 g ch phm, thm 20 ml nc, lc trong 30 pht v lc. Lay 10 ml dch lc, thm 0,1 ml dung dch phenolphtalein (TT) lm ch th. Khng c dng qu 0,2 ml dung dch natri hydroxyd 0,1 M (C) lm chuyn mu ca ch th.

Sulfathiazol v cc amin thm bc mtHa tan 5 mg ch phm trong hn hp c lm lnh n 15 c gm 3,5 m\ nc, 6 ml dung dch acid hydrocloric long (TT) v 25 ml ethanol 96 % (TT). Nhng ngay vo nc v thm 1 ml d u n g d c h natri nitrit 0,25 %. yn 3 pht, thm 2,5 ml dung dch acid suphamic % v yn trong 5 pht. Thm 1 ml dung dch naphthylethylendiamin dihydroclorid 0,4 % v pha long thnh 50 ml vi nc, thu c dung dch th.Song song chun b dung dch chun: Ly 1 ml dung dch c cha 10 mg sulfathiazol chun (C) v 0,5 ml acid hydrocloric (TT) trong 100 ml; thm 2,5 ml nc, 6 ml dung dch acid hydrocloric long (TT) v 25 ml vi ethanol 96 % (TT). Tin hnh tng t nh vi dung dch th . hp th nh sng ti bc sng 550 nm (Ph lc4.1) ca dung dch th khng c ln hn hp th ca dung dch chun,

Kim loi nngKhng c qu 20 phn iu (Ph lc 9,4.8).

Ly 1,0 g ch phm tin hnh th theo phng php 3. Dng 2 ml dung dch ch mu 10 phn iu (TT) chun b mu i chiu.

M t khi lng do lm khKhng c qu 2,0 % (Ph lc 9.6).(1,00 g; 100 c n 105 C). '

Tro SulfatKhng c qu 0,1 % (Ph lc 9.9, phng php 2). Dng 1,0 g ch phm.

nh ingHa tan 0,300 g ch phm trong 40 ml dmethyl- formamid (TT), thm 0,2 ml dung dch thymolphtalein (TT). Chun bng dung dch natri hydroxyd 0,1 N (C) cho n khi mu ca ch th chuyn sang mu xanh lam. Song song tin hnh mu trng.1 ml dung dch natri hydroxyd 0,1 N (C) tng ng vi 20,17 mg C17H 13N 3O5S2 .

Bo qunTrnh nh sng.

Loi thucKhng khun.

VIN NN PHTHALYLSULFATHIAZOL Tabellae PhthalylsufathiazoliL vin nn cha phthalylsulfathiazol.Ch phm phi p ng cc yu cu trong chuyn lun Thuc vin nn (Ph lc 1.20) v cc yu cu sau y:

Hm lng phthalylsulfathiazol, C 17H 13N 3O 5S2, t95,0 % n 105,0 % so vi hm lng ghi n nhn.

Tnh chtVin mu trng, khng mi.

inh tnhChit mt lng bt vin tng ng vi 1,5 g phthalyl- sulfathiazol vi 60 ml aceton (TT) nng, lc v bc hi dch lc n kh. sy cn 105 c, dng cn thu c th cc phn ng sau:A, Cn thu c phi cho phn ng D quy nh ong phn nh tnh ca chuyn lun "Phthalylsulfathiazor'.B. Ly 1 g cn, thm 8,5 ml dung dch natri hydroxyd2 M (TT), un si di sinh hn hi lu trong 30 pht. ngui v thm 17,5 ml dung dch acd hydrocloric long (TT). Lc k v lc. Trung ha dch lc bng dung dch natri hydroxy 2 M (TT). Lc, ra ta bng nc. Kt tinh li bng nc v sy cc tinh th thu c 100 c n 105 c. Ha tan 10 mg tinh th trong 200 ml dung dch acid hydrocloric 0,1 M (TT),2 ml dung dch thu c cho phn ng nh tnh ca amin thom bc nht (Ph lc 8.1) vi ta vng hnh thnh.

c. Ly 10 mg cn, thm 20 mg phenol (TT) v 3 git acd sulfuric m c (TT), un n khi hn hp c mu nu. ngui, thm 20 ml nc v kim ha bng dung dch natri hydroxyd 2 M (TT), c mu hng xut hin (phn ng phn bit vi sucinyl- sulfathiazol).

SulfathiazolLc k mt lng bt vin nghin mn tng ng vi 7,5 mg phthalylsulfathiazol trong mt hn hp gm 25 ml ethanol 96 % (TT), 6 ml dung dch acid hydrocorie long (TT) v 3,5 m nc c lm lnh trc n 15 c ri lc. Lm lnh ngay dch lc trong nc v thm vo dch lc 1 m dung dch natr ntrit 0,25 %, trn u v yn trong 3 pht. Thm 2,5 ml dung dch acid sulfamic 4 %, yn tip trong 5 pht. Thm 1 ml dung dch N-(l-naphthyl) ethyendamin dhydroclorid 0,4 % v pha long n va 50 ml vi nc. hp th (Ph lc 4 .1) ca dung dch thu c 550 im khng c ln hn hp th ca dung dch i chiu c chun b ng thi, trong cng iu kin nh sau: Dng mt hn hp gm 25 ml ethanol 96 % (TT), 2 ml nc, 6 ml dung dch acid hydroclorc long (TT) v 1,5 ml dung dch c chun b bng cch ha tan 10 mg sulfathiazol v 0,5 ml acid hydrocloric m c (TT) trong nc va 100 mL Lm lnh ngay hn hp thu c trong nc , thm vo hn hp 1 ml dung dch natri nitrit 0,25 %, trn u v yn trong 3 pht. Tin hnh nh trn, bt u t 'T h m 2,5 ml dung dch acid sulfamic 4 % ...

nh lngCn 20 vin, tnh khi lng trung bnh vin, nghin thnh bt mn. Cn chnh xc mt lng bt vin toTig ng vi khong 0,5 g phthalylsulfathiazol, cho vo mt bnh cu nh, thm 2 0 ml acd hydrocloric m c (TT) v 10 ml nc ri un si di ng sinh hn hi lu trong 1 gi. Dng 20 m dung dch acid hydroclorc long (TT) chuyn ton b lng cht lng trong bnh thy phn sang mt cc dung tch 200 ml. Tin hnh chun bng nitrit (Ph lc 10,4).1 ml dung dch natr ntrt 0,1 M (C) tng ng vi 40,34 mg C]7Hi3N3 0 5 S2 .

Bo qunng trong chai l nt kn. ni kh, mt, trnh nh sng.

Loi thuc Khng khun.

Hm lng thng dng 500 m g.'

PHYTOMENADIONPhytomenadionum Vitamin K l

h Me h" Me

C31H46O2 p.t.l: 450,71

Phytomenadion l hn hp ca 2-m ethyl-3-[(2)- (7 ^ ,1 7 ,1 l,154etram ethylhexadec-2-enyI]naph-thalen -1,4-dion (fraw5-phytomenadion), 2-methyl-3- [(2Z)-(7i,l l,15-tetram ethylhexadec-2-enyl]-naphthalen-1 ,4-dion (cw-phyto menadion) v 2,3- epoxy"2-methyl-3-[(2E)~(7R,l 1R )-3J511,15-te am eth yl hexadec-2-enyl]"2,3-dihydronaphthalen-1 ,4-dion (trans- epoxyphytomenadion). Cha khng qu 4,0 % trms- epoxyphytomenadion v khng t hon 75,0 % ans- phytomenadion. Tng ca 3 thnh phn kling c t hn 97,0 % v khng c nhiu hn 103,0 %.

Tnh chtCht lng dng du nht, trong v mu vng hoc vng cam, khng mi.D tan trong ether, iso octan, cloroform v du bo.Hi tan trong ethanol 96 % v methanol, thc t khng tan trong nc. N b phn hy dn dn v b sm mu do nh sng.Ch s khc x khong 1,526 .

nh tnhTin hnh nhanh chng v trnh tc ng ca nh sng.A. Ha tan 10,0 mg ch phm trong trmethylpentan (TT) pha long thnh 100,0 ml vi cng dung mi. Ph t ngoi (Ph lc 4 .1) ca dung dch thu c trong vng t 275 nm n 340 nm cho hp th cc i 327 nm v cc tiu 285 nm. A (1 %; 1 cm) bc sng cc i phi t 67 n 73.Pha long tip 10 ,0 ml dung dch trn thnh 50,0 ml vi trimethylpentan (TT). Ph t ngoi (Ph lc 4.1) ca dung dch ny trong vng t 230 nm n 280 nm, cho 4 hp th cc i 243 nm, 249 nm, 261 nm v 270 nm.B. Trong sc k th Menadion v cc tp cht lin quan khc: v t chnh ca dung dch th (2) phi tng t v v tr, mu sc v kch thc vi vt chnh ca dung dch i chiu (1) .c . Ha tan 50 mg ch phm trong 10 ml methanol (TT) v thm 1 ml dung dch kali hydroxyd 20 %

trong m ethanol, mu xanh lc xut hin v tr nn tm khi un nng trong cch thy 40 c v sau chuyn sang mu nu .

trong ca dung dchHa tan 2,5 g ch phm trong trimethylpentan (TT) v pha long thnh 25 ml vi cng dung mi. Dung dch phi trong (Ph lc 9.2).

Ch s acidKhng qu 2,0 (Ph lc 7.2) (dng 2,00 g ch phm).

Menadion v cc tp cht lin quan khcXc nh bng phng php sc k lp mng (Ph lc5.4).Bn mng: Silica gel GF254.Dung mi khai trin'. Cyclohexan - toluen (20 : 80). Dung dch th (1): Ha tan 0j40 g ch phm trong cyclohexan (TT) v pha long thnh 10 ml vi cng dung mi.Dung dch th (2): Pha long 1 ml dung dch th (1) thnh 10 ml vi cyclohexan (TT).Dung dch i chiu ()\ Ha tan 40 mg phytomenadion chun ong cyclohexan (TT) v pha long thnh 10 ml vi cng dung mi.Dung dch i chiu (2)\ Pha long 1 ml dung dch th(2) thnh 20 ml bng cycohexan (TT).Dng dch i chiu (3): Ha tan 4,0 mg menadion (TT) trong cyclohexan (TT) v pha long thnh 50 ml vi cng dung mi.Cch tin hnh: Chm ring bit ln bn mng 10 |uil mi dung dch trn. Trin khai sc k n khi dung mi i c khong 15 cm, ly bn mng ra, kh ngoi khng kh trong 5 pht. Quan st di nh sng t ngoi bc sng 254 nm v phun dung dch acid phosphomolybdic 10 % trong ethanol (TT). sy bn mng 120 c trong 5 pht.Quan st di nh sng thng. Trn sc k ca dung dch th ( 1 );Bt c vt no tong ng menadion khng c m mu hn vt trn sc k ca dung dch i chiu(3) (0,2 %); Bt c vt no, khc vt chnh v vt tng ng vi menadion, khng c m mu hofn vt ca dung dch i chiu (2) (0,5 %). B qua bt c vt no nm di vt chnh v khng tch hon ton khi vt chnh.

Tro SulfatKhng c qu 0,1 % (Ph lc 9.9, phng php 2). Dng 1,0 gch phm.

nh lngPhng php sc k lng (Ph lc 5.3).Pha ng'. Octanol - di-isopropyl ether - heptan (0,67 : 3,3:1000)Dung dch th: Ha tan 15,0 mg ch phm trong pha ng v pha long thnh 1 0 , 0 ml vi pha ng.

Dung dch i chiu (1): Ha tan 15,0 mg phyto- menadion chun trong pha ng v pha long thnh1 0 , 0 ml vi pha ng.D m dch i chiu (2): Ha tan 15,0 mg phytomenadin chun v 4,0 mg trans-epoxyphytomenadion chun trong pha ng v pha long thnh 1 0 , 0 ml vi pha niu kin sc k:C t th p k h n g g 0 ,2 5 ra X 4 ,6 m m c n h i spherical silica gel dng cho sc k (5 |xm) vi l xp 8 nm.Tc dng: 0,4 ml/min.Detector quang ph t ngoi t ti bc sng 254 nm. Th tch tim: 20 f^ l.Tim dung dch i chiu (2). iu chnh nhy ca h thng sao cho chiu cao ca pic chnh t nht bng 50 % ca thang o.Php th ch c gi tr khi th t ra gii ca cc pic l /ra5 -epoxyphytomenadion, c-phytomenadion v /ra5 -phytomenadion. Tin hnh tim dung dch i chiu (1) 6 ln. Php nh lng ch c gi tr khi lch chun tng i ca din tch pic ng phn trans nh hn 1 , 0 % v phn gii gia pic tng n vi ra5 -phytomenadion v c-phytomenadion t nht l 2,5. Tim dung dch th v dung dch i chiu ( 1 ), tnh ton nng phn trm ca trans- phytomenadion, c/-phytomenadion v /rara-epoxyphy- tomenadion theo cc cng thc sau:

m ' X A'trans ^ Strans rran 5 -phytomenadion = --------------------------

m X S'tr

C-phytomenadion

trans - epoxyphytomenadion

cis

m X s \epoxy

Trong :m' l khi lng (mg) cht chun trong dung dch i chiu ( 1 );m l khi lng (mg) ch phm trong ung dch th; A'trans l hm lng (%) ra5-phytomenadion trong phytomenadion chun;A'cis l hm lng (%) c-phytome nadion trong phytomenadion chun;A 'epoxy l hm lng (%) ans - epoxyphytomenadion ong phytomenadion chun;Strans l in tch pic tng ng vi ng phn trans trong sc k ca dung dch th;Scis l din tch pic tng ng vi ng phn cis trong sc k ca dung dch th;Sepoxy l din tch pic tong ng vi ng phn trans epoxyphytomenadion - trong sc k ca dung dch th;

Strans l din tch pic tng ng vi ng phn -ans trong sc k ca dung dch i chiu ( 1 );Scis l din tch pic tng ng vi ng phn cis trong sc k ca dung ch i chiu ( 1 );S'epoxy l din tch pic tng ng vi ng phn trans- epoxyphytomenadion trong sc k ca dung dch i chiu ( 1).

Bo qunTrong bao b kn, trnh nh sng.

Loi thucTng t vitamin K.

Ch phmThuc tim, vin nn.

VIN NN PHYTOMENADIONTabellae Phytomenadioni

L vin nn nhai hay ngm cha phytomenadion.Ch phm phi p ng cc yu cu trong chuyn lun Thuc vin nn (Ph lc 1.20) v cc yu cu sau y:

Hm lng phytomenadion, C31H46O2, t 90,0 % n 1 1 0 , 0 % so vi lng ghi trn nhn.

Tnh chtVin c mu ng nht.

nh tnhLc mt lng bt vin tng ng vi 50 mg phyto- menadion vi 50 ml ethanol (TT), khong 1 gi, lng. Ly 5 ml ch trong cho vo bnh nh mc 50 ml, thm ethanol (TT) n nh mc, lc u (dung dch A). Ph hp th (Ph lc 4.1) ca dung dch A trong khong bc sng t 230 nm n 350 nm, phi c cc i