Validation of a rapid and sensitive LC-MS/MS method for determination of exemestane and its metabolites, 17β-hydroxyexemestane and 17β-hydroxyexemestane-17-O-β-D-glucuronide: application to human pharmacokinetics study

PloS One
Ling-Zhi WangBoon-Cher Goh

Abstract

A novel, rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the evaluation of exemestane pharmacokinetics and its metabolites, 17β-dihydroexemestane (active metabolite) and 17β-dihydroexemestane-17-O-β-D-glucuronide (inactive metabolite) in human plasma. Their respective D3 isotopes were used as internal standards. Chromatographic separation of analytes was achieved using Thermo Fisher BDS Hypersil C18 analytic HPLC column (100 × 2.1 mm, 5 μm). The mobile phase was delivered at a rate of 0.5 mL/min by gradient elution with 0.1% aqueous formic acid and acetonitrile. The column effluents were detected by API 4000 triple quadrupole mass spectrometer using electrospray ionisation (ESI) and monitored by multiple reaction monitoring (MRM) in positive mode. Mass transitions 297 > 121 m/z, 300 > 121 m/z, 299 > 135 m/z, 302 > 135 m/z, 475 > 281 m/z, and 478 > 284 m/z were monitored for exemestane, exemestane-d3, 17β-dihydroexemestane, 17β-dihydroexemestane-d3, 17β-dihydroexemestane-17-O-β-D-glucuronide, and 17β-dihydroexemestane-17-O-β-D-glucuronide-d3 respectively. The assay demonstrated linear ranges of 0.4-40.0 ng/mL, for exemestane; and 0.2-15.0 ng/mL, for 17β-dihydr...Continue Reading

References

Aug 1, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eric P WinerGeorge P Browman
Jul 12, 2007·Clinical Journal of Oncology Nursing·Loren WintersJoan Gallagher
Jan 1, 2008·Cancer Treatment Reviews·Andrea EisenKathleen I Pritchard
May 27, 2008·Clinical Breast Cancer·Christina I Herold, Kimberly L Blackwell
Jul 16, 2008·Expert Opinion on Drug Metabolism & Toxicology·Per Eystein Lønning, Jürgen Geisler
Sep 30, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Landry K KamdemZeruesenay Desta
Mar 26, 2011·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Seiki TakashimaShozo Ohsumi
May 3, 2011·Steroids·Gustavo de Albuquerque CavalcantiFrancisco Radler de Aquino Neto
Sep 16, 2011·Expert Review of Anticancer Therapy·Federica TomaoSilverio Tomao
Nov 16, 2011·Breast Cancer : Basic and Clinical Research·Muaiad Kittaneh, Stefan Glück
May 17, 2012·Therapeutic Advances in Medical Oncology·Jennifer Keating LittonBanu K Arun
May 29, 2012·Asian Pacific Journal of Cancer Prevention : APJCP·Sun Hye KimJungsil Ro
Aug 3, 2012·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·Yang ZhangJill M Kolesar
Jan 11, 2013·Japanese Journal of Clinical Oncology·Melissa C C Teo, Khee Chee Soo
Jan 18, 2014·Endocrine-related Cancer·Kathleen Van AstenRobert Paridaens

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Citations

Mar 20, 2016·The Journal of Steroid Biochemistry and Molecular Biology·Ana Filipa SobralNatércia Teixeira
May 24, 2017·The Pharmacogenomics Journal·S LuoP Lazarus
Jun 5, 2018·Clinical Pharmacokinetics·Stefanie L GroenlandNeeltje Steeghs
Jul 28, 2020·Breast Cancer Research and Treatment·Vikki HoUNKNOWN MAP3 Investigators

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