Development and validation of LC-MSMS assay for the determination of the prodrug dabigatran etexilate and its active metabolites in human plasma

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Eman G NoumanHayam M Lotfy

Abstract

Dabigatran etexilate (DABE) is a low-molecular-weight prodrug that is converted after oral administration to dabigatran (DAB)-a directly acting oral anticoagulant. In this study, an LC-MSMS assay was developed and validated for the determination of DABE, free DAB and its equipotent O-glucuronide conjugates in plasma. Owing to the susceptibility of DABE and DAB to chemical hydrolysis, cleavage of the O-glucuronide moiety was carried out using β-glucuronidase enzyme. Free and total plasma concentrations of DAB were determined in incurred plasma samples before and after enzymatic cleavage (50°C and 3 h), respectively. RP-HPLC separation was carried out using acetonitrile: water (30:70, v/v), adjusted to pH 3.0 using formic acid. Tandem mass spectrometric detection at positive electrospray ionization in the MRM mode was then employed for the determination of DABE and DAB. The analysis was carried out within 5.0 min over a linear concentration range of 1.00-600.00 ng/mL for the prodrug and its active metabolite. Validation was carried out according to FDA guidelines for bioanalytical method. The recoveries were higher than 89.48%, the accuracy was within 98.33-110.12% and the RSD was below 10% for the studied compounds in both incur...Continue Reading

References

Mar 20, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·James E PatrickMitchell N Cayen
Nov 17, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Stefan BlechWilly Roth
Nov 17, 2009·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Rolf W SparidansJos H Beijnen
Jun 17, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Thomas EbnerWolfgang Wienen
Oct 1, 2010·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·M KolmonenI Ojanperä
Jan 5, 2011·Biomedical Chromatography : BMC·Wenkui LiFrancis L S Tse
Jul 15, 2011·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Tina TrdanAleš Mrhar
Jan 19, 2012·European Journal of Clinical Pharmacology·Andreas ClemensSebastian Härtter
Nov 12, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Naoki IshiguroOlaf Schaefer
Nov 13, 2013·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Ji DongLiyan Miao

❮ Previous
Next ❯

Citations

Mar 23, 2017·Clinical Chemistry and Laboratory Medicine : CCLM·Martin H J WiesenCarsten Müller
Sep 17, 2019·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·L SlavikM Palova

❮ 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.