[液相色谱-串联质谱法测定人血浆中的氯诺昔康]

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

作者信息

Zeng Ya-lin, Chen Xiao-yan, Zhang Yi-fan, Zhong Da-fang

机构信息

Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, Shenyang 110016, China.

出版信息

Yao Xue Xue Bao. 2004 Feb;39(2):132-5.

PMID:15127622

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.

摘要

目的

建立一种灵敏、特异的液相色谱-串联质谱法测定人血浆中氯诺昔康，并研究单剂量氯诺昔康在健康中国志愿者体内的药代动力学。

方法

采用液-液萃取法从血浆中提取氯诺昔康和内标吡罗昔康，然后在Zorbax XDB-C8柱上进行分离。流动相为甲醇-水-甲酸（80:20:0.5），流速为0.7 mL·min-1。使用配备大气压化学电离源的Finnigan TSQ串联质谱仪作为检测器，以正离子模式运行。分别采用m/z 372→121和m/z 332→121的前体离子→产物离子组合进行选择反应监测（SRM）来定量氯诺昔康和内标。

结果

在2.0～1600 μg·L-1浓度范围内获得线性校准曲线。定量限为2.0 μg·L-1。该方法成功应用于氯诺昔康的药代动力学研究。18名中国男性志愿者口服8 mg氯诺昔康后的主要参数如下：T1/2值为（4.7±1.1）h，AUC0-∞为（5.5±2.4）mg·h·L-1。然而，另一名志愿者的T1/2为105 h，AUC0-∞为189.5 mg·h·L-1。