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In analytical sample preparation, extraction and leaching of chemical compounds from syringe filters are major concerns particularly when using Liquid
Chromatography/Mass Spectrometry (LCMS) for analysis. An underlying issue when filtration is used for sample preparation is the need to reduce the
amount of extractable and leachable compounds in the syringe filter effluents that may ultimately jeopardize analytical results and data interpretation.
Two common issues related to filtration for LCMS sample preparation are the presence of extraneous chromatographic peaks and ion suppression/
enhancement. The former could result in co-elution of extractable and leachable compounds with analytes of interest. The latter, also known as matrix
effects (ME), is of particular concern to LCMS users utilizing the most versatile and commonly used MS interface - Electrospray Ionization (ESI).
To address these concerns, Pall Corporation has developed a new Acrodisc® MS syringe filter, which is certified for low extractables using a highly
sensitive LCMS method. This syringe filter exhibits excellent compatibility and is made of high quality water-wettable polytetrafluoroethylene (WWPTFE)
membrane and high-density polyethylene (HDPE) housing materials.
The development of the Acrodisc MS syringe filters is presented in this study. In addition, the cleanliness of filter effluents using Pall’s Acrodisc MS syringe
filters and two commercially available alternative syringe filters were compared by evaluating the presence of extractable/leachable compounds in the
filter effluents under the same filtration and LC/ESI/MS analytical test conditions. Moreover, the ME (ion suppression/enhancement) due to potentially
interfering extractable/leachable compounds were studied for the analyses of three drug substances by comparing the MS signal intensity of each drug
substance spiked into the filter effluent against a control solution using fast gradient LC/ESI/MS.
Optimized Materials of Construction
Filter Media: WWPTFE membrane
Housing: Specially chosen HDPE
Key Properties (25 mm Discs)
Pore Size Rating: 0.2 µm
Effective Filtration Area: 3.9 cm2
Maximum Operating Pressure and Temperature: 60 psi at 21-24 ºC (70-75 °F),
30 psi at 55 ºC (131 °F)
Typical Water Flow Rate: 140 mL/min at 30 psi
Cleanliness: Verified by LCMS using an internal procedure
LCMS (ES+) Total Ion Current Chromatograms of Effluents Using Various Fluids
*System peak on each chromatogram
Filters were soaked in each solvent for 24 hours under ambient conditions.
Analyzed using UPLC/UV/MS method capable of detecting 50 ppb of various polymer additives.
UV data and ES(-) data (not presented) also showed cleanliness of the effluents.
Compatibility of Acrodisc MS SyringeFilters with Various Chemicals
Total of 51 chemicals were tested ( not all results are shown).
No visual defects (e.g. swelling, color change) and significant changes in bubble point after 48 hr. soak were observed.
LCMS AnalysisConditions: UPLC Gradient Method. Detection: ES(+)/MS. Mass Range: 100-1400 amu.
Column: ACQUITY� UPLC BEH C18, 1.7 µm (Waters Corporation), Mobile Phase: A (MeOH +
0.01% FA) and B (Water + 0.01% FA). FA – Formic Acid, MEOH - Methanol.
Test Fluids: Acetonitrile (ACN), 50:50 (v/v) ACN:Water, Methanol (MeOH), 50:50 (v/v)
MeOH:Water
Products Tested: Acrodisc MS Filters, Competitor A (PVDF Filters), Competitor B
(Hydrophilic PTFE Filters). Competitor products evaluated have low-extractable claims.
Total Ion Current Chromatograms of the Effluents
Competitor A filters are not compatible with ACN, and were therefore not
tested using this solvent.
Products Tested: Acrodisc MS syringe filters, Competitor A (PVDF filters), Competitor B
(hydrophilic PTFE filters). Competitor products evaluated have low extractable claims.
Matrix Effect (ME) was evaluated using the following equation:
% ME = Response in Filtered Solution
x 100 Response in Unfiltered Solution (Control)
where % ME = 100 - no matrix effect, > 100% ion enhancement and < 100% ion suppression
Matrix Effects Observed for Each Analyte
Note: Dashed lines (---) indicate no matrix effect (i.e. % ME = 100)
A new, unique syringe filter with broad chemical compatibility and low extractable/leachable materials has been developed for LCMS applications by Pall
Corporation. This study demonstrates that Acrodisc MS syringe filters are an excellent choice for LCMS sample preparation using aqueous, mild organic
solvents, and mixtures thereof.
Note: This work was completed using a 25 mm Acrodisc MS syringe filter. The product is also available in a 13 mm version suitable for samples as small
as 25 µL.
Development of Low Extractable Syringe Filters for Liquid Chromatography/Mass Spectrometry Applications
Gilbert E. Tumambac, Weibing Ding, and Larry Scheer; Pall Corporation, Ann Arbor, MI USA
ABSTRACT EFFLUENT CLEANLINESS UNDER VARIOUS CONDITIONS
PRODUCT DEVELOPMENT
© 2013, Pall Corporation. Pall, , and Acrodisc are trademarks of Pall Corporation. ® indicates a trademark registered in the USA. �ACQUITY UPLC is a trademark of
Waters Corporation. 2/13, GN13.8468
SUMMARY AND CONCLUSIONS
CLEANLINESS STUDIES
MembraneMaterials
Preselection Based on Physical and Chemical Properties
Extractables Analysis by LCMS
Optimized Product
Product Quali!cation Cleanliness and Matrix Effect Studies
HousingMaterials
CH2CI2
0.01N HCI
Acetonitrile
Methanol
Water
*
Acids
Alcohols
Bases
Esters
Ethers
Glycols
Hydrocarbons (HC)
Halogenated HCs
Oils
Ketones/Aldehydes
Others
VisualExam
Soak For 48 Hours Under Ambient Condiditon
Integrity Test by Bubble Point
Integrity Test by Bubble Point
{
G
lacial
Ace
tic A
cid
Acetic
Acid
, 30%
(v/v)
Hydro
chlor
ic Acid
, 12N
(Con
c.)
Nitr
ic Acid
, 16N
(Con
c.)
Sulf
uric
Acid, 3
7N (C
onc.)
Ben
zyl A
lcoho
l
Eth
anol
I
sopro
panol
M
etha
nol
A
mm
onium
Hyd
roxid
e, 6N
S
odium
Hyd
roxid
e, 6N
n-But
yl Ace
tate
Cell
osolv
e Ace
tate
E
thyl
Aceta
te
Eth
yl Eth
er
Tet
rahy
drofu
ran
Ethyle
ne G
lycol
Propyle
ne G
lycol
Tolue
ne
X
ylene
s
C
hloro
form
Met
hylen
e Chlo
ride
Te
trach
loroe
thyle
ne
A
ceto
ne
M
ethy
l Eth
yl Ket
one (
MEK)
Pea
nut O
il
Ace
tonit
rile
Dim
ethy
lsulfo
xide (
DMSO)
H
exan
es, d
ry
1
8 Meg
ohm
-cm
Wat
er-20
0
20
40
60
% C
hang
e in
Bub
ble
Poi
nt
Chemical Name
Collect ~ 2 mL ef�uent
25 mm Syringe Filtersn = 10 per vendor
50:50 MeOH:Water MeOH 50:50 ACN:Water
ACN
OPTIMIZED PRODUCT
CHEMICAL COMPATIBILITY
CHEMICAL COMPATIBILITY MATRIX EFFECT STUDIES
Collect ~ 2 mL ef�uent
25 mm Syringe Filtersn = 25 per vendor
MeOH
Pool Samples
Mometasome Furoate
Verapamil
Acetaminophen
Analytes in Un!ltered MeOH
Conditions: Ballistic UPLC gradient method. Detection: selected ion recording (SIR), ES(+)/MS for MometasoneFuroate and Verapamil, ES(-)/MS for Acetaminophen. Column:ACQUITY UPLC BEH C18, 1.7 µm), Mobile phase: A (MeOH +0.01% FA) and B (Water + 0.01% FA).
COMPETITOR B
COMPETITOR A
PALL
CONTROL
Inte
nsity
Mometasone Furoate
Verapamil
Acetaminophen
SIR Chromatogram Showing Ion Suppression at 1 PPMMometasone Furoate
Contact Phone: 800.521.1520 (USA and Canada) • (+)800.PALL.LIFE (Outside USA and Canada) • www.pall.com/lab • E-mail: [email protected]