A sensitive, fast and accurate liquid chromatography–electrospray ionization-tandem mass spectrometry (LC–MS/MS) method for the pharmacokinetic study of cyclobenzaprine tablets

Abstract

A simple, fast and accurate liquid chromatography–electrospray ionization-tandem mass spectrometry method was developed and validated for the quantification of cyclobenzaprine in human plasma. After a simple single-step liquid–liquid extraction with ethyl acetate, the analyte was separated in an Intersil ODS-3 column through isocratic elution with methanol–water containing 0.1% formic acid (80:20, v/v) at a flow rate of 0.2 ml/min and analyzed by mass spectrometry in the positive ion MRM mode. Good linearity was achieved from 0.04 to 50 ng/ml. The intra- and interday precisions were less than 12.1%, and accuracy ranged from 99.6 to 106.2%. The elimination half-lives (t1/2 Z) after a single oral administration of 5, 10, and 15 mg cyclobenzaprine tablets were 25.5, 26.2, and 26.4 h, respectively. The means ofCmax and AUC increased proportionally to the cyclobenzaprine doses. The pharmacokinetics of cyclobenzaprine fit the linear dynamics of the cyclobenzaprine dose range in healthy Chinese volunteers. Key words: Cyclobenzaprine, liquid chromatography, electrospray ionization, tandem mass spectrometry.