An improved LC-MS/MS method for simultaneous evaluation of CYP2C9, CYP2C19, CYP2D6 and CYP3A4 activity

Bioanalysis
Santosh Kumar Sreevatsav AdirajuSussan Ghassabian

Abstract

To develop an LC-MS/MS assay to quantitate well-tolerated substrates; midazolam (CYP3A), omeprazole (CYP2C19), dextromethorphan (CYP2D6), losartan (CYP2C9) and their respective metabolites' concentrations in plasma samples. A solid-phase extraction method was optimized to extract analytes of interest simultaneously from human plasma samples. The assay analyzed plasma samples collected from patients who received equal or lower than therapeutic doses of CYP substrates. This assay was validated based on the European Medicines Agency guideline for bioanalytical method validation and was sensitive, linear, accurate and precise with acceptable recovery and matrix effects. Small sample volume and dose of cytochrome P450 substrates, short-run time, using stable isotope internal standards and being cost effective are the major advantages of the assay.

References

Jun 18, 2003·Clinical Pharmacology and Therapeutics·Magnus ChristensenLeif Bertilsson
Apr 10, 2012·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Kyung-Suk OhDong-Hyun Kim
Apr 12, 2014·Clinical Pharmacology and Therapeutics·M BosilkovskaY Daali

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