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High‐throughput LC‐MS/MS assay for 6‐methoxy‐2‐naphthylacetic acid, an active metabolite of nabumetone in human plasma and its application to bioequivalence study
Author(s) -
Patel Bhavin N.,
Sharma Naveen,
Sanyal Mallika,
Prasad Arpana,
Shrivastav Pranav S.
Publication year - 2008
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.1047
Subject(s) - chemistry , chromatography , analyte , detection limit , bioequivalence , selected reaction monitoring , tandem mass spectrometry , mass spectrometry , nabumetone , liquid chromatography–mass spectrometry , active metabolite , metabolite , analytical chemistry (journal) , pharmacokinetics , medicine , biochemistry , nonsteroidal , pharmacology
A simple, precise and accurate assay for the determination of 6‐methoxy‐2‐naphthylacetic acid (6‐MNA), an active metabolite of nabumetone in human plasma, was developed and validated using liquid chromatography–tandem mass spectrometry (LC‐MS/MS). The analyte (6‐MNA) and propranolol (internal standard, IS) were extracted from 200 µL aliquot of human plasma via solid‐phase extraction employing HLB Oasis cartridges and separated on a Discovery ® HS C 18 (50 × 4.6 mm, 5 µm) column. Detection of analyte and IS was done by tandem mass spectrometry with a turbo ion spray interface operating in positive ion and multiple reaction monitoring acquisition mode. The total chromatographic runtime was 3.0 min with retention time for 6‐MNA and IS at 1.97 and 1.26 min, respectively. The method was validated over a dynamic linear range of 0.20–60.00 µg/mL for 6‐MNA with mean correlation coefficient r ≥ 0.9986. The intra‐batch and inter‐batch precision (%CV) across five validation runs (lower limit of quantiation, low‐, medium‐ and high‐quality controls and upper limit of quantitation) was less than 7.5%. The accuracy determined at these levels was within −5.8 to +0.2% in terms of percentage bias. The method was successfully applied for a bioequivalence study of 750 mg nabumetone tablet formulation in 12 healthy Indian male subjects under fasted condition. Copyright © 2008 John Wiley & Sons, Ltd.