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LC-MS in Drug Discovery
Timothy V. Olah, Ph.D.
Director, Bioanalytical ResearchPharmaceutical Research Institute
Bristol-Myers Squibb Company
University of Connecticut20 February 2007
Wallingford, CT: Virology: HIV (AIDS), Hepatitis C, CNS: Anxiety, Depression, Alzheimer’s, Migraine
Lawrenceville, NJ: Oncology: CancerImmunology: Rheumatoid Arthritis, Asthma
Hopewell, NJ:Cardiovascular: Thrombosis, Atherosclerosis Metabolic Diseases: Diabetes, Obesity
Drug Discovery Programs at BMS
Wallingford:
Deborah Barlow, Marc Browning, Mike Donegan, Daniel
Morgan, Kim Snow, Sarah Taylor, Kim Widmann
Lawrenceville:
Hollie Booth, Chris Caporuscio, Georgia Cornelius,
Celia D'Arienzo, Lorell Discenza, Mohammed Jemal, Zheng
Ouyang, Asoka Ranasinghe, Bogdan Sleczka, Yi Tao, Xia Yuan,
Jian Wang, Steven Wu
Hopewell:
Hong Cai, Cecilia Chi, Jim Smalley, Minjuan Wang, Richard
Wong, Baomin Xin, Carrie Xu, Hongwei Zhang, Joanna Zheng
BMS Bioanalytical Research
Bioanalytical Research Staffing
• Personnel: 30 scientists• Location: WFD (7), LVL (13), HPW
(9) • Mass Spectrometers : 30 MS/MS• Full Phase Programs: 34• Early Phase Programs: 25 • Research Initiatives• Samples 1-4Q 2006: ~184,000
145795
184056
84335
139789
6567256618
0
25000
50000
75000
100000
125000
150000
175000
200000
2001 (7) 2002 (10) 2003 (14) 2004 (19) 2005 (19) 2006 (20)
Total samples
Total Number of Samples Analyzed by BAR (FTE) in Support of Discovery
BAR-Discovery Annual Sample Count
767373556024
6567
9203
1672
2225
25332632
1730
0
500
1000
1500
2000
2500
3000
2002 (10) 2003 (14) 2004 (19) 2005 (19) 2006 (20)
com
po
un
ds
anal
yzed
-500
1000
2500
4000
5500
7000
8500
10000
sam
ple
s p
er a
nal
yst
per BAR FTE Compounds
Outline
• LC-MS in Drug Discovery
• Drug Discovery Process
• Strategies and Work Flow Processes• Development and Implementation of Multiple
Component LC-MS-based Bioanalytical Methods
• Examples, Questions, Comments• What is of interest to you today in regards to
the Pharmaceutical Industry ?
Bioanalytical Research’s Goal
To generate accurate and precise data in the quantitative analysis of drug discovery candidates in samples from in vivo and in vitro studies that support their biological characterization and optimization as potential development candidates.
The Gilbert Bioanalytical Chronicles
“The challenges of bioanalysis stem from the need to accurately and reproducibly measure part per million to part per trillion quantities of analyte in complex biological matrices, full of
potentially interfering endogenous or drug-related substances.”
John Gilbert et al., “High Performance Liquid Chromatography with Atmospheric Pressure Ionization Tandem Mass Spectrometry as a Tool in Quantitative Bioanalytical
Chemistry,” in Biochemical and Biotechnological Applications of Electrospray Ionization Mass Spectrometry, American Chemical Society (1995)
Relative Amounts
1.0 gram
0.001 gram (milligram)
0.000001 gram (microgram)
0.000000001 gram (nanogram)
0.000000000001 gram (picogram)
Stages of Drug Discovery and Development
Discovery - Nomination PreClinical - Clinical
GLP
Compound
Factors for Consideration• Bioanalytical Method Requirements• Application of Technologies• Risk Assessment
Drug Discovery Process
Bioassays: Potency / Selectivity
New Chemical Entities from Medicinal Chemistry
ADME Characteristics
In Vitro and / or In Vivo
Experiments
Data Interpretation
Reporting
Sample Analysis
Information Management
High Throughput Screening
Automation
A
B
C
D
E
F
G
HPhysical Properties
ExperimentalDesign
Drug Discovery Process
Bioassays: Potency / Selectivity
New Chemical Entities from Medicinal Chemistry
ADME Characteristics
In Vitro and / or In Vivo
Experiments
Data Interpretation
Reporting
Sample Analysis
Information Management
High Throughput Screening
Automation
A
B
C
D
E
F
G
HPhysical Properties
ExperimentalDesign
Relationship of Drug Metabolism with Medicinal
Chemistry in Early Drug Discovery
• Add information to compliment HTS data
• Assist in the selection of compounds based upon their ADME characteristics for further evaluation
• Provide direction to medicinal chemists for the design of their next compound in a series
• Identify trends in the architecture of a class of compounds that correlates with a response in an ADME assay (e.g. Potency with P450 inhibition)
Stomach
LiverSystemicCirculati
on
Portal Vein
“Absorption, Distribution, Metabolism, Excretion”
Intestine
Duodenum
(Excretion)
(Absorption)
(Distribution) (Metabolism)
Kidney
Desirable ADME Characteristics
Absorption - good solubility and permeability
Distribution - good exposure at the target, minimal elsewhere- acceptable protein binding: estimate “free concentration”
Metabolism- minimal first pass effect- metabolism by two or more CYP (not 2D6) to few metabolites- minimal potential to inhibit or to induce
Excretion- balance between metabolism and excretion of parent drug
Experiments to Assess ADME Characteristics
Absorption- Caco-2 cells, PAMPA, PgP-transport- in vivo PK profiling
• Distribution- in vitro protein binding, in vivo tissue distribution studies
• Metabolism- Metabolic stability in microsomes, S9 fractions, hepatocytes- P450 Inhibition: microsomes and/or rCYPs, co-administration- P450 Induction: Gene Chips, PXR, multiple dosing studies- Metabolite characterization
• Excretion- Quantitation of drugs and metabolites in biological fluids
BAR Responsibilities
• Analyze samples from in vivo studies:
– Early Exposure (Biology), Coarse PK, Full PK, PK/PD, Tissue Distribution, “Bioequivalence”, TK (CV Telemetry, Pre-ECN, ECN) …
– Co-Administration: Screening (N-in-one), P450 Inhibition, Marker Compounds, Stable Label…
– All routes of administration (IV, PO, IP, SQ, IN…)
– All types of formulations by Pharmaceutics.
BAR Responsibilities
• Analyze samples from in vitro studies:
– serum protein binding, tissue binding, serum/plasma/chemical stability…
– intrinsic clearance, P450 inhibition, pgP, PAMPA, Caco-2…
– biological assays, heart/liver perfusion…
BAR Responsibilities
• Analyze samples in all types of species and biological matrices:
– mice, rats, marmoset, guinea pig, rabbit, dogs, monkeys, chimp, human…
– blood, plasma, serum, urine, bile, CSF, SV, brain, lung, heart, liver, GI tract, kidney, muscle, tumor, adipose tissue…
– microsomes, hepatocytes, S9 fractions, rCYP, incubation systems, mixed matrices, buffers, dosing solutions…
BAR Responsibilities
• Rapidly develop and implement multiple component bioanalytical methods using LC-MS/MS-based detection.
– Analyte and Internal Standard
– Analyte(s) and Internal Standard(s)
• Co-Administration Studies, Pro-Drugs
– Parent Compound, Metabolite(s), IS
– Parent Compound, Distinct Equilibrium Forms
the TIME required to generate data
the quality of DATA required to
generate meaningful results
the type of RESULTS that are
requested in the screen
Keys to Developing Successful
Screening Strategies
TIME
DATA RESULTS
“Scaling” Annual BAR Output: Number of Compounds Evaluated• 10,000 - 30,000 evaluated in “Screens”
• 1000 - 3000 evaluated in “Early Phase”
• 100 - 300 evaluated in detail “Full Phase”
• 10 - 30 evaluated for “Nomination”
• 1 - 3 compounds “NDA” approved
Bioanalytical Work Flow
Method Developme
nt
Sample Receipt/Tracking
Preparation of Analytical
Standards & QCs
Sample Preparation
Notebooks and Ancillary Data
Reporting
Data Processing
Sample Analysis
Information Management
LC-MS/MS
Standard Operating Guidelines
A
B
C
D
E
F
G
H
ProgrammingAutomation
What is LC-MS?(LC) Liquid Chromatography:
Chromatography is a separations method that relies on differences in partitioning behavior between a flowing mobile phase and a stationary phase to separate the components in a mixture.
A column holds the stationary phase and the mobile phase carries the sample through it.
Sample components that partition strongly into the stationary phase spend a greater amount of time in the column and are separated from components that stay predominantly in the mobile phase and pass through the column faster.
(www.chem.vt.edu/chem-ed/ac-meths.html)
HPLC Analysis
0
meaningful data
X time
Gradient
Elution
Recondition
What is LC-MS?
(MS) Mass Spectrometry:Mass spectrometers use the difference in mass-to-charge ratio (m/z) of ionized compounds to separate them from each other. Compounds have distinctive fragmentation patterns that provide structural information to specifically detect compounds.
(www.chem.vt.edu/chem-ed/ac-meths.html)
Types of Mass Spectrometers
• LC-MS (single quadrupole)• LC-MS/MS (triple quadrupoles)• LC-Q (ion traps, linear ion traps)• LC-Q-TRAPS (quadrupole linear ion
traps)• LC-TOF-MS (time-of-flight)• MALDI-TOF-MS • Q-TOF-MS (quadrupole time-of-flight)• FT-MS (Fourier Transform)• Others
Uses of Mass Spectrometry in Drug Discovery
• Qualitative AnalysisElucidation of the structural characteristics of various substances in different matrices:
What is in the sample?
• Quantitative AnalysisDetermination of the concentration of various substances in different matrices:
How much is in the sample?
O
NH
SO
O
NH2
OH
O
N
O NH2
O
N
N
N
S
N
O
O
OO
N
DiltiazemC22H26N2O4S
MW = 414.2 Da.
BumetanideC17H20N2O5S
MW = 364.1 Da.
CarbamazepineC15H12N2O
MW = 236.1 Da.
PyrilamineC17H23N3O
MW = 285.2 Da.
NH
ON
O
O
O
O
O
O
O
O
ReserpineC33H40N2O9
MW = 608.3 Da.
N
N
O
O
NN
O
O
Cl Cl
Ketoconazole (ISTD)C26H28N4O4Cl2
MW = 530.1 Da.
Types of MS Detection Methods
• Full Scan Spectra• Selected Ion Monitoring• Product Ion Spectra• Neutral Loss Scans• Multiple Reaction Monitoring• Accurate Mass Measurements• Others
SulfasalazineC18 H14 N4 O5 SMW 398.40
N NH
S N N
O O
OH
C OH
O
+Q1: 5 MCA scans from sulfasalazine_FinalQ1_Pos.wiff Max. 7.4e6 cps.
396.5 397.0 397.5 398.0 398.5 399.0 399.5 400.0 400.5 401.0 401.5m/z, amu
0.0
5.0e5
1.0e6
1.5e6
2.0e6
2.5e6
3.0e6
3.5e6
4.0e6
4.5e6
5.0e6
5.5e6
6.0e6
6.5e6
7.0e6
7.4e6
Inte
nsity, cp
s
399.0
400.0
400.9 401.1
Full Scan Spectrum
+Product (399.0): Experiment 3, 0.345 to 1.047 min from 049-IS Sulfasalazine MSMS.wiff Max. 9.3e5 cps.
60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400m/z, amu
0.0
5.0e4
1.0e5
1.5e5
2.0e5
2.5e5
3.0e5
3.5e5
4.0e5
4.5e5
5.0e5
5.5e5
6.0e5
6.5e5
7.0e5
7.5e5
8.0e5
8.5e5
9.0e5
Inte
ns
ity, c
ps
223.2
119.0
213.1
94.0 147.1239.0
165.3
137.1 381.1240.8316.9
287.2157.1 169.0 185.391.0 257.0224.3333.2111.1 121.1
N NH
S N N
O O
OH
C OH
O
m/z 137m/z 165
m/z 94
m/z 119
m/z 223
Product Ion Spectrum
Multiple Reaction Monitoring
+
+ ES Ionization
+
++
++
+++
+
+
+
++
Collisiongas
11.5 12 12.5 13 13.5 14 14.5
MRM Transitionm/z – m/z
Q1 – Fixedprecursor m/z
(m/z “x”)
Q3 – Fixedproduct m/z
(m/z “y”)
Q2 – Collisionchamber
Ar
Ar+
+
+
Multiple Reaction Monitoring
+
+ ES Ionization
+
++
++
+++
+
+
+
++
Collisiongas
11.5 12 12.5 13 13.5 14 14.5
MRM Transitionm/z 339 – m/z 223
Q1 – Fixedprecursor m/z
(m/z 399)
Q3 – Fixedproduct m/z
(m/z 223)
Q2 – Collisionchamber
Ar
Ar+
+
+
XIC of +MRM (1 pair): 399.1/223.0 amu from Sample 35 (z020923a035) of Linearity_ISTD.wiff, Sm... Max. 2.5e4 cps.
0.85 0.90 0.95 1.00 1.05 1.10 1.15 1.20 1.25 1.30 1.35 1.40 1.45 1.50 1.55 1.60 1.65 1.70 1.75Time, min
0.0
2000.0
4000.0
6000.0
8000.0
1.0e4
1.2e4
1.4e4
1.6e4
1.8e4
2.0e4
2.2e4
2.4e4
2.6e42.7e4
Inte
ns
ity, c
ps
1.22
Inte
nsit
y ( c
ps)
Time (min)
Multiple Reaction Monitoring:specific precursor / product ion pair399 m/z -> 223 m/z
Plasma Extract SIM: m/z 603
Plasma Extract SIM: m/z 617
Plasma Extract MRM: m/z 603-> m/z 483
Plasma Extract MRM: m/z 617-> m/z 483
Full Scan Spectrum
200 250 300 350 400 450 500 550 600 650 700m/z0
100
%
BMS-724296 13 (0.247) Cm (9:15) Scan ES+ 5.00e6492.37
336.28
220.23299.07
245.13
377.27
387.01
494.25
524.49565.11 647.04 690.86
732.56
Precursor Ion
Product Ion Spectrum
100 150 200 250 300 350 400 450 500 550m/z0
100
%
BMS-724296 D 18 (0.339) Cm (8:18) Daughters of 492ES+ 1.25e7336.11
233.95120.38 140.06
Multiple Reaction Monitoring: two analytes
(m/z 492 -> m/z 336), (m/z 539 -> m/z 332)
1.50 2.00 2.50 3.00 3.50 4.00Time0
100
%
0
100
%
S102504 PK 026 MRM of 6 Channels ES+ 539.07 > 332
1.60e52.03
S102504 PK 026 MRM of 6 Channels ES+ 492.1 > 336.15
2.04e51.89
IS
BMS-724296
Multiple Reaction Monitoring (m/z 492 -> m/z 336)
Multiple Reaction Monitoring (m/z 539 -> m/z 332)
Examples of the Use of Multiple Component LC-MS/MS-based Bioanalytical Methods in Drug
Discovery
• Determination of Drugs and Metabolites
• Co-Administration Studies
Bioanalytical Method for Determination of
BMS-xxxxx and Metabolites in Biological Fluids to Support the Diabetes Program
Structures
R
Cl
R
Cl
OH
R
Cl
O
Parent Compound
MW=392.88
“Alcohol” Metabolite
MW=408.88
“Ketone” Metabolite
MW=406.88
“Styrene” Metabolite
MW=390.87
R
Cl
Mass Spectrometry:Negative Ion Electrospray
Multiple Reaction Monitoring
Parent
Styrene Metabolite Ketone Metabolite Alcohol Metabolite Diol Metabolite Internal Standard
Multiple Component Bioanalytical Method
Function Reaction Dwell(secs)* Cone Volt. Col.Energy 2 391.5 > 313.1 0.2 45 15 2 389.4 > 311.1 0.2 45 15 1 405.6 > 327.7 0.1 40 15 1 407.8 > 329.9 0.1 40 15 1 423.3 > 333.5 0.1 45 20 1 379.5 > 289.21 0.1 45 30
STD 10K in FFA/FFB (Neat Soln.)
1.00 2.00 3.00 4.00 5.00 6.00 7.00Time0
100
%
655956METAB070604002 MRM of 5 Channels ES- TIC
7.59e52.69
3.63
Diol Metabolite
Alcohol
Ketone
Styrene
Parent Compound
Chromatography Requirements
Due to isotopic interferences there was a need for chromatographic separation of the parent compound and the metabolites.
Chromatography RequirementsSTD 10K in FFA/FFB (Neat Soln.)
0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 5.50 6.00 6.50 7.00Time0
100
%
0
100
%
0
100
%
0
100
%
0
100
%
655956METAB070604002 MRM of 5 Channels ES- 423.34 > 333.55
7.59e52.69
655956METAB070604002 MRM of 5 Channels ES- 407.8 > 329.99
1.65e53.37
655956METAB070604002 MRM of 5 Channels ES- 405.59 > 327.65
4.85e53.63
655956METAB070604002 MRM of 5 Channels ES- 391.5 > 313
3.28e54.76
655956METAB070604002 MRM of 5 Channels ES- 389.38 > 311.13
2.36e54.53
Isotopic interference from Ketone
Parent Compound
Styrene Metabolite
Ketone Metabolite
Alcohol Metabolite
Diol Metabolite
Isotopic interference from Styrene
BMS-XXXXXProdrug and Metabolites
O
O
O
O
N
O
O
O
O
OO
O
O
OO
O
O
O
O
Prodrug, M+H+ =514
Metab M+H+ =385
Parent, M+H+ =457
Metab M+H+ =473
Metab M+H+ =487
A representative chromatogram with all of the required separations achieved
XIC of +MRM (6 pairs): 457.1/236.0 amu from Sample 41 (Sample_770780_1) of Metabolites.wiff (Turbo Spray) Max. 1.7e5 cps.
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5Time, min
0.0
5.0e4
1.0e5
1.5e5
2.0e5
2.5e5
3.0e5
3.5e5
4.0e5
4.5e5
5.0e5
5.5e5
5.9e5
Inte
ns
ity, c
ps
3.19
Time B% 0.01 45 0.80 70 3.00 85 3.10 95 4.10 95 4.20 45 5.50 Stop
API-4000, +MRM
Column: Atlantis dC18, 3uM, 2.1x50mm
Mobile phase:
A: H2O, 0.1%FA
B: ACN, 0.1%FA
Flow rate: 0.3ml/min
a
c
b
d
e
What are “Co-Administration” Studies? (Cassette Dosing / N-in-One Studies)
Simultaneous administration of multiple compounds (including a standard compound) to individual animals with the subsequent determination of the concentrations of each compound contained within single test samples.
1000
1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 9.00Time0
100
%
0
100
%
0
100
%
0
100
%
0
100
%
0
100
%
010401_007 MRM of 12 Channels ES+ 386.1 > 264.1
9.22e66.90
010401_007 MRM of 12 Channels ES+ 370.1 > 300.1
1.96e77.46
010401_007 MRM of 12 Channels ES+ 399 > 329
2.48e77.89
010401_007 MRM of 12 Channels ES+ 390 > 320
2.29e77.68
010401_007 MRM of 12 Channels ES+ 473 > 266.2
1.97e64.36
010401_007 MRM of 12 Channels ES+ 370.1 > 314.2
3.71e65.09
SRM Chromatograms of Plasma Extract from a Dog Dosed with 20 Substances Simultaneously
Bioanalytical Work Flow
Method Developme
nt
Sample Receipt/Tracking
Preparation of Analytical
Standards & QCs
Sample Preparation
Notebooks and Ancillary Data
Reporting
Data Processing
Sample Analysis
Information Management
LC-MS/MS
Standard Operating Guidelines
A
B
C
D
E
F
G
H
ProgrammingAutomation
Method Development
• LC-MS/MS-based Methods
– MS parameters are established for every analyte
– HPLC conditions required for adequate response,
specificity and sensitivity
– Preparation of biological samples is critical to the
integrity and quality of the method• Analyte response will differ in different biological extracts
• Differentiates Bioanalytical from Analytical
Preparation of Standard and
Quality Control (QC) Samples
• Known quantities of the compounds to be evaluated are added to blank biological matrix at established concentration ranges
• Internal Standard is added to Standard, QC, and Test samples
• Standard, QC, and Test samples are then processed in an identical manner
• All of the samples are then analyzed and the standard and QC samples are used to assess assay performance in terms of accuracy and precision
How do we assess variability of our analytical methods in drug
discovery?Standard Curve
(ng/mL) Six QCs at 5 Concentrations
1000
500
200
100
50
20
10
5
2
1
Accuracy & Precision at
LOQ
Accuracy & Precision
Over Linear Range
Assay Integrity
• Determined by Standard and QC results in conjunction with analytical requirements of the study
• Alternative method development is carried out, as needed– Modifications to MS parameters,
chromatography, sample preparation procedures, Internal Standard selection, assay dynamic range, etc.
• Goal to provide quality data in all analysis
Quality Control Data for ‘Compounds A and B’
Compound A (LOQ = 2.5 ng/mL)
Low (2.5 ng/mL)
Mid (5 ng/mL)
Mid (10 ng/mL)
Mid (50 ng/mL)
High (500 ng/mL)
Mean 2.74 5.32 9.84 50.44 507.75
S.D. 0.43 0.76 1.28 3.04 53.64
%CV 15.69 14.29 13.01 6.03 10.56
%Theoretical 109.6 106.4 98.4 100.9 101.6
n 6 6 6 6 6
Compound B (LOQ = 5.0 ng/mL)
Low
(2.5 ng/mL)
Mid (5 ng/mL)
Mid (10 ng/mL)
Mid (50 ng/mL)
High (500
ng/mL)
Mean 2.10 4.79 10.03 51.55 529.65
S.D. 1.07 0.82 1.36 1.93 22.99
%CV 50.95 17.12 13.56 3.74 4.34
%Theoretical
84.0 95.8 100.3 103.1 105.9
n 6 6 6 6 6
‘Compound X’ Fails Quality Control Requirements
Run Date
Low (1ng/mL)
Mid (2 ng/mL)
Mid (5 ng/mL)
Mid (10 ng/mL)
Mid (50 ng/mL)
High (500 ng/mL)
Mean -1.31 1.19 3.44 8.29 61.83 543.21
S.D. 1.12 3.31 2.67 3.58 21.15 98.78
%CV -85.50 278.15 77.62 43.18 34.21 18.18
%Theoretical -131.0 59.5 68.8 82.9 123.7 108.6
n 6 6 5 4 5 5
HPLC Analysis
0
meaningful data
X time
Peaks are sent to the MS for only 1/4 of the total run time,
leaving the MS idle for 3/4 of the time.
Gradient
Elution
Recondition
PumpPump
PumpPump
PumpPump
PumpPump
Detector(MS)
Detector(MS)
AutosamplerAutosampler
HPLC
HPLC
HPLC
HPLC
0 4min
Multiplexed HPLC systems to Single MS/MS
Switching valve
System1
System2
System3
System4
System1
Staggered Parallel Analysis
Mass spectrometer data collection
XIC of +MRM (3 pairs): 328.1/231.2 amu from Sample 13 (STD 625) of ASMS GABA std curve 8May06.wiff (Turbo Spray) Max. 2.2e5 cps.
0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4 2.6 2.8 3.0Time, min
0.0
1.0e4
2.0e4
3.0e4
4.0e4
5.0e4
6.0e4
7.0e4
8.0e4
9.0e4
1.0e5
1.1e5
1.2e5
1.3e5
1.4e5
1.5e5
1.6e5
1.7e5
1.8e5
1.9e5
2.0e5
2.1e5
2.2e5
Inte
ns
ity, c
ps
0.62
0.59
Conventional HPLC
UPLC
Resolved glucuronidesignal
TFC
Retention time and resolution comparison between UPLC, TFC, and HPLC analysis
RT: 0.00 - 8.00
0 1 2 3 4 5 6 7 8Time (min)
0
50
1000
50
1000
50
1000
50
100
Re
lativ
e A
bund
ance 0
50
1000
50
1005.97
4.18
5.974.68
4.67
4.17
4.49
2.06
6.29
NL: 4.02E6TIC F: + c SRM ms2 [email protected] [ 232.10] MS gr_cyno_A_06
NL: 5.27E5TIC F: + c SRM ms2 [email protected] [ 343.20] MS gr_cyno_A_06
NL: 1.26E5TIC F: + c SRM ms2 [email protected] [ 163.00] MS gr_cyno_A_06
NL: 1.03E5TIC F: + c SRM ms2 [email protected] [ 121.00] MS gr_cyno_A_06
NL: 1.98E4TIC F: + c SRM ms2 [email protected] [ 225.10] MS gr_cyno_A_06
NL: 6.91E6TIC F: + c SRM ms2 [email protected] [ 336.10] MS gr_cyno_A_06
Simultaneous Quantitation of Drugs and Endogenous “Biomarkers”
BMS-Compound
Prednisolone
Cortisone
Cortisol
Triamcinolone (IS)
BMS-(IS)
Summary
• Bioanalytical Research (BAR)
• Drug Discovery Process
• ADMET Characteristics
• BAR Responsibilities
• LC-MS/MS in Drug Discovery
• Types of Analysis
• Future Directions
Wallingford:
Deborah Barlow, Marc Browning, Mike Donegan, Daniel
Morgan, Kim Snow, Sarah Taylor, Kim Widmann
Lawrenceville:
Hollie Booth, Chris Caporuscio, Georgia Cornelius,
Celia D'Arienzo, Lorell Discenza, Mohammed Jemal, Zheng
Ouyang, Asoka Ranasinghe, Bogdan Sleczka, Yi Tao, Xia Yuan,
Jian Wang, Steven Wu,
Hopewell:
Hong Cai, Cecilia Chi, Jim Smalley, Minjuan Wang, Richard
Wong, Baomin Xin, Carrie Xu, Hongwei Zhang, Joanna Zheng
BMS Bioanalytical Research
