Esterase inhibitors as ester-containing drug stabilizers and their hydrolytic products: potential contributors to the matrix effects on bioanalysis by liquid chromatography/tandem mass spectrometry

Rapid Communications in Mass Spectrometry : RCM
Naiyu ZhengJianing Zeng

Abstract

Esterase inhibitors are widely used to stabilize ester-containing drugs in biological matrices for quantitative liquid chromatography/tandem mass spectrometry (LC/MS/MS) assays. These co-existing inhibitors could cause matrix effects on bioanalysis and jeopardize the assay performance. We therefore developed an LC/MS/MS methodology to monitor the fate of inhibitors and evaluate their matrix effects, which is described in this study. Human plasma containing 20 mM of diisopropylfluorophosphate (DFP), paraoxon, eserine, phenylmethylsulfonyl fluoride (PMSF) or 2-thenoyltrifluoroacetone (TTFA) was extracted by liquid-liquid extraction (LLE) and analyzed by an LC/MS/MS assay for BMS-068645 (a model drug) with additional pre-optimized selected reaction monitoring (SRM) transitions using positive/negative electrospray ionization (ESI) mode for each inhibitor. Hydrolytic products were characterized by product ion or neutral loss scan LC/MS/MS analysis. The matrix effect contribution from each inhibitor was evaluated by post-column infusion of BMS-068645. In the extracted samples by LLE, SRM chromatograms revealed the presence of paraoxon, eserine and TTFA with peak intensity of >2.50E08. Three DFP hydrolytic products, diisopropyl phosph...Continue Reading

References

Aug 1, 1997·Biological & Pharmaceutical Bulletin·S TakaiK Hirano
Nov 10, 2000·Journal of the American Society for Mass Spectrometry·R KingT Olah
Mar 20, 2002·Current Topics in Medicinal Chemistry·Bradley L AckermannAnthony T Murphy
Apr 16, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tetsuo SatohBert N La Du
May 7, 2002·Biochemical Pharmacology·Jin Gang Zhang, Marc W Fariss
Jan 28, 2003·Therapeutic Drug Monitoring·Maria ShipkovaEberhard Wieland
Feb 6, 2004·Journal of Pharmaceutical Sciences·Mahesh N SamtaniWilliam J Jusko
Sep 22, 2005·Therapeutic Drug Monitoring·Jiwen Chen, Yunsheng Hsieh
May 17, 2006·Drug Metabolism and Pharmacokinetics·Satoshi YamaoriKazuhito Watanabe
Jun 22, 2006·Current Drug Metabolism·Mohammed Jemal, Yuan-Qing Xia
Jan 24, 2007·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Erin ChambersJeffrey R Mazzeo
Mar 16, 2007·Journal of Pharmaceutical and Biomedical Analysis·Raymond Naxing XuTawakol A El-Shourbagy
May 24, 2007·Analytical and Bioanalytical Chemistry·Franck Saint-MarcouxPierre Marquet
Mar 29, 2008·Expert Opinion on Drug Metabolism & Toxicology·Yunsheng Hsieh
Apr 3, 2008·Journal of Pharmaceutical Sciences·Shiori TakahashiTsuyoshi Yokoi
Oct 24, 2009·Journal of Pharmaceutical and Biomedical Analysis·Matthias KoitkaHans-Hubert Borchert
Jan 5, 2011·Biomedical Chromatography : BMC·Wenkui LiFrancis L S Tse
Jun 18, 2011·Bioanalysis·Matthew Ewles, Lee Goodwin

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.