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.
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 microL aliquot of human plasma via solid-phase extraction employing HLB Oasis cartridges and separated on a Discovery HS C18 (50 x 4.6 mm, 5 microm) 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 microg/mL for 6-MNA with mean correlation coefficient r > or = 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.
Patel
Bhavin N
BN
Chemistry Department, School of Sciences, Gujarat University, Navrangpura, Ahmedabad-380 009, India.
Sharma
Naveen
N
Sanyal
Mallika
M
Prasad
Arpana
A
Shrivastav
Pranav S
PS
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D002074:Butanones / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods*; D018592:Cross-Over Studies; D005215:Fasting / Q000097:blood; D006801:Humans; D008297:Male; D000077430:Nabumetone; D009280:Naphthaleneacetic Acids / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D052616:Solid Phase Extraction / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013810:Therapeutic Equivalency
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D009280:Naphthaleneacetic Acids; C044612:6-methoxy-2-naphthylacetic acid; D000077430:Nabumetone