[Determination of lornoxicam in human plasma by LC/MS/MS]

Abstract

Aim: To develop a sensitive and specific LC/MS/MS method for determination of lornoxicam in human plasma and investigate pharmacokinetics of single dose of lornoxicam in healthy Chinese volunteers.

Methods: Lornoxicam and the internal standard piroxicam were extracted from plasma using liquid-liquid extraction, then separated on a Zorbax XDB-C8 column. The mobile phase consisted of methanol-water-formic acid (80:20:0.5) at a flow-rate of 0.7 mL.min-1. A Finnigan TSQ tandem mass spectrometer equipped with atmospheric pressure chemical ionization source was used as detector and operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor-->product ion combinations of m/z 372-->121 and m/z 332-->121 was used to quantify lornoxicam and internal standard, respectively.

Results: The linear calibration curves were obtained in the concentration range of 2.0-1,600 micrograms.L-1. The limit of quantitation was 2.0 micrograms.L-1. The method was successfully used in the pharmacokinetic study for lornoxicam. The main parameters obtained after an oral dose of 8 mg lornoxicam to 18 Chinese male volunteers were as follows: the value of T1/2 was (4.7 +/- 1.1) h, AUC0-infinity was found to be (5.5 +/- 2.4) mg.h.L-1. However, T1/2 of 105 h and AUC0-infinity of 189.5 mg.h.L-1 were obtained for another volunteer.

Conclusion: The method is proved to be suitable for clinical investigation of lornoxicam pharmacokinetics, which offers advantages of specificity, speed, and higher sensitivity over the previously reported methods.