A5054768892- Mass Spectrometry Techniques and Applications
- Analytical Chemistry and Chromatography
- Pharmacogenetics and Drug Metabolism
- Drug Transport and Resistance Mechanisms
- Metabolomics and Mass Spectrometry Studies
- Biosimilars and Bioanalytical Methods
- Pharmacological Effects and Toxicity Studies
- Advanced Biosensing Techniques and Applications
- Antibiotics Pharmacokinetics and Efficacy
- Analytical chemistry methods development
- Metabolism and Genetic Disorders
- Biosensors and Analytical Detection
- Pesticide Residue Analysis and Safety
- Microfluidic and Capillary Electrophoresis Applications
- Advanced Proteomics Techniques and Applications
- Genetics, Bioinformatics, and Biomedical Research
- Liver Disease Diagnosis and Treatment
- Eicosanoids and Hypertension Pharmacology
- Monoclonal and Polyclonal Antibodies Research
- Computational Drug Discovery Methods
- Data Quality and Management
- Pharmacological Effects of Natural Compounds
- Pharmaceutical and Antibiotic Environmental Impacts
- MicroRNA in disease regulation
- Quality Function Deployment in Product Design
Pfizer (United States)
2002-2023
Vertex Pharmaceuticals (United States)
2022
Hyundai Mobis (South Korea)
2017
Medical Oncology Hematology Consultants
2013
Bristol-Myers Squibb (United States)
2008-2012
Bristol-Myers Squibb (Germany)
2010-2012
PSG Institute of Medical Sciences & Research
2011
Merck & Co., Inc., Rahway, NJ, USA (United States)
2010
University of Nottingham
2007
Post Graduate Institute of Medical Education and Research
2000
Abstract It can be argued that the last true paradigm shift in bioanalytical (BA) arena was from high‐performance liquid chromatography (HPLC) with ultraviolet (UV) detection to HPLC tandem mass spectrometry (MS/MS) after commercialization of triple quadrupole spectrometer 1990s. HPLC‐MS/MS analysis based on selected reaction monitoring (SRM) has become gold standard for BA assays and is used by all major pharmaceutical companies quantitative new drug entities (NCEs) as part discovery...
To address the most appropriate endogenous biomarker for drug–drug interaction risk assessment, eight healthy subjects received an organic anion transporting polypeptide 1B (OATP1B) inhibitor (rifampicin, 150, 300, and 600 mg), a probe drug cocktail (atorvastatin, pitavastatin, rosuvastatin, valsartan). In addition to coproporphyrin I, widely studied OATP1B biomarker, we identified at least 4 out of 28 compounds (direct bilirubin, glycochenodeoxycholate‐3‐glucuronide,...
This study describes the application of liquid chromatography/mass spectrometry (LC/MS) methods for distinguishing between aliphatic and aromatic hydroxylations N-oxidations. Hydroxylations N-oxidations are common biotransformation reactions drugs. Electrospray (ESI) atmospheric pressure chemical ionization (APCI) were used to generate ions from chromatographic effluents. ESI-MS, ESI-MS/MS, APCI-MS, APCI-MS/MS experiments performed on several metabolites derivatives loratadine (a long-acting...
A new method is described for performing hydrogen/deuterium (H/D) exchange in an electrospray ionization (ESI) source. The use of liquid chromatography (LC)-mass spectrometer equipped with ESI source and deuterium oxide (D2O) as the sheath allows H/D experiments to be performed on-line. This directly provides information determining number position exchangeable hydrogens, aiding elucidation structures drug metabolites. To demonstrate utility this method, LC-mass spectrometry (MS) LC-MS/MS...
Endogenous biomarkers are emerging to advance clinical drug‐drug interaction (DDI) risk assessment in drug development. Twelve healthy subjects received a multidrug and toxin exclusion protein (MATE) inhibitor (pyrimethamine, 10, 25, 75 mg) crossover fashion identify an appropriate endogenous biomarker assess MATE1/2‐K‐mediated DDI the kidneys. Metformin (500 was also given as reference probe for MATE1/2‐K. In addition previously reported candidates (creatinine N 1 ‐methylnicotinamide...
The aim of this study was to investigate the sensitivity and specificity endogenous glycochenodeoxycholate glycodeoxycholate 3-O-glucuronides (GCDCA-3G GDCA-3G) as substrates for organic anion transporting polypeptide 1B1 (OATP1B1) in humans. We measured fasting levels plasma GCDCA-3G GDCA-3G using liquid chromatography-tandem mass spectrometry 356 healthy volunteers. mean both compounds were ~ 50% lower women than men (P = 2.25 × 10-18 P 4.73 10-9 ). In a microarray-based genome-wide...
The widely different LC-MS response observed for many structurally compounds limits the use of in full scan detection mode quantitative determination drugs and metabolites without using reference standard. recently introduced nanospray ionization (NSI) technique shows comparable MS some under non-LC-MS conditions. However, presence numerous endogenous commonly associated with biological samples such as urine, plasma, bile, is required to separate, detect, identify, measure individual...
The 2016 10th Workshop on Recent Issues in Bioanalysis (10th WRIB) took place Orlando, Florida with participation of close to 700 professionals from pharmaceutical/biopharmaceutical companies, biotechnology contract research organizations, and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event – A Full Immersion Week including Biomarkers Immunogenicity. As usual, it specifically designed facilitate sharing, reviewing, discussing agreeing approaches address the most...
The 15th edition of the Workshop on Recent Issues in Bioanalysis (15th WRIB) was held 27 September to 1 October 2021. Even with a last-minute move from in-person virtual, an overwhelmingly high number nearly 900 professionals representing pharma and biotech companies, contract research organizations (CROs), multiple regulatory agencies still eagerly convened actively discuss most current topics interest bioanalysis. WRIB included 3 Main Workshops 7 Specialized that together spanned week...
Vorapaxar (SCH 530348), a potent oral thrombin protease-activated receptor 1 antagonist, is being developed as an antiplatelet agent for patients with established vascular disease. The objective of this study was to identify the human liver cytochrome P450 (P450) enzyme(s) responsible metabolism SCH 530348. Human microsomes metabolized 530348 M19, amine metabolite formed via carbamate cleavage, and M20 (monohydroxy-SCH 530348). Recombinant CYP3A4 exhibited most activity (11.5% profiled...
The 2017 11th Workshop on Recent Issues in Bioanalysis (11th WRIB) took place Los Angeles/Universal City, California from 3 April to 7 with participation of close 750 professionals pharmaceutical/biopharmaceutical companies, biotechnology contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event - A Full Immersion Week Bioanalysis, Biomarkers Immunogenicity. As usual, it specifically designed facilitate sharing, reviewing, discussing...
The 2018 12th Workshop on Recent Issues in Bioanalysis (12th WRIB) took place Philadelphia, PA, USA April 9-13, with an attendance of over 900 representatives from pharmaceutical/biopharmaceutical companies, biotechnology contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day full immersion bioanalysis, biomarkers immunogenicity. As usual, it specifically designed to facilitate sharing, reviewing, discussing agreeing approaches address the most current...
The 2019 13th Workshop on Recent Issues in Bioanalysis (WRIB) took place New Orleans, LA, USA April 1–5, with an attendance of over 1000 representatives from pharmaceutical/biopharmaceutical companies, biotechnology contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, week-long event – full immersion week bioanalysis, biomarkers, immunogenicity gene therapy. As usual, it specifically designed to facilitate sharing, reviewing, discussing agreeing...
There is a growing interest in using endogenous compounds as drug transporter biomarkers to facilitate drug–drug interaction (DDI) risk assessment early phase I clinical trials. Compared other transporters, however, no valid biomarker for hepatic organic cation (OCT) 1 has been described date. The present work represents the first report of an compound, isobutyryl-l-carnitine (IBC), potential OCT1 DDI assessment. A hydrophilic chromatography (HILIC)-mass spectrometry/high resolution mass...
The present study demonstrated that in addition to CYP3A4 and CYP2D6, the metabolism of loratadine is also catalyzed by CYP1A1, CYP2C19, a lesser extent CYP1A2, CYP2B6, CYP2C8, CYP2C9 CYP3A5. biotransformation was associated with formation desloratadine (DL) further hydroxylation both DL parent drug (loratadine). Based on inhibition correlation studies contribution CYP2C19 major circulating metabolite seems be minor. Reported clinical results suggest steady state mean (%CV) plasma Cmax...
Background: UHPLC coupled with orthogonal acceleration hybrid quadrupole-TOF (Q-TOF)-MS is an emerging technique offering new strategies for the efficient screening of chemical entities and related molecules at early discovery stage within pharmaceutical industry. In first part this article, we examine main instrumental parameters that are critical integration UHPLC–Q-TOF technology to existing bioanalytical workflows, in order provide simultaneous quantitative qualitative bioanalysis...
Aim: The application of high-resolution MS to antibody–drug conjugate (ADC) drug development may provide insight into their safety and efficacy. Quantification unconjugated cytotoxic (payload) characterization drug-to-antibody ratio distribution were determined in plasma using orthogonal acceleration quadrupole-time-of-flight MS. Results: Unconjugated payload quantification by quadrupole-time-of-flight-based MRMhighresolution triple quadrupole-based multiple reaction monitoring comparable...
Aim: A validated LC–MS/MS assay for the quantitation of coproporphyrin-I and -III (CP-I, CP-III) in human plasma has been developed to understand utility both as possible endogenous biomarkers organic anion-transporting polypeptides (OATP)-mediated drug–drug interactions (DDIs). Materials Methods: Human extracts were analyzed CP-I CP-III using a Sciex API 6500+ mass spectrometer. Results: The was utilized samples from clinical DDI study involving new chemical entity that presented an OATP...
In the pharmaceutical industry, a higher attrition rate during drug discovery process means lower failure in later stages. This translates into shorter development time and reduced cost for bringing to market. Over past few years, analytical strategies based on liquid chromatography/mass spectrometry (LC/MS) have gone through revolutionary changes presently accommodate most of needs industry. Among these LC/MS techniques, collision induced dissociation (CID) or tandem mass (MS/MS MS(n))...
The absorption, metabolism and excretion of carbon-14-labeled loratadine (LOR, SCH 29851, Claritin) administered orally to healthy male volunteers were evaluated. Following a single oral 10-mg dose [(14)C]LOR ( approximately 102 microCi), concentrations LOR desloratadine (DL; pharmacologically active descarboethoxy metabolite LOR) determined in plasma. Metabolites plasma, urine feces characterized using liquid chromatography-mass spectrometry system (LC-MS) connected line with flow...