液相色谱-质谱-质谱联用法测定人血浆中氯诺昔康液相色谱-质谱-质谱联用法测定人血浆中氯诺昔康

目的建立测定人血浆中氯诺昔康的液相色谱-质谱-质谱联用法,并用于中国受试者口服氯诺昔康的体内药代动力学研究。方法血浆样品经液-液萃取后,以甲醇-水-甲酸(80∶20∶0.5)为流动相,吡罗昔康为内标,采用Zorbax XDB-C8柱分离,通过液相色谱串联质谱,以选择反应监测(SRM)方式进行检测。定量分析离子反应分别为m/z 372→121(氯诺昔康)和m/z 332→121(吡罗昔康)。结果线性范围为2.0～1 600 μg·L^-1,定量下限为2.0 μg·L^-1。18名受试者po氯诺昔康8 mg后主要药动学参数t_1/2为(4.7±1.1) h,AUC_0-∞为(5.5±2.4) mg·h·L^-1。而另一名受试者t_1/2为105 h,AUC_0-∞为189.5 mg·h·L^-1。结论该法灵敏度高,线性范围宽,操作简便、快速,适用于临床药代动力学研究。

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

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.