液相色谱-质谱-质谱联用法测定人血浆中氯诺昔康  

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

作　　者：曾亚琳[1] 陈笑艳[1] 张逸凡[1] 钟大放[1] 

机构地区：[1]沈阳药科大学药物代谢与药物动力学实验室,辽宁沈阳110016

出　　处：《药学学报》2004年第2期132-135,共4页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目 ( 39930 1 80 )

摘　　要：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∶2 0∶0 5)为流动相 ,吡罗昔康为内标 ,采用ZorbaxXDB 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 3 72→ 12 1(氯诺昔康 )和m z 3 3 2→ 12 1(吡罗昔康 )。结果　线性范围为 2 0～ 160 0 μg·L- 1,定量下限为 2 0μg·L- 1。 18名受试者po氯诺昔康 8mg后主要药动学参数T1 2 为 (4 7± 1 1)h ,AUC0 -∞ 为 (5 5± 2 4)mg·h·L- 1。而另一名受试者T1 2 为 10 5h ,AUC0 -∞ 为 189 5mg·h·L- 1。结论　该法灵敏度高 ,线性范围宽 ,操作简便、快速 。Aim To develop a sensitive and specific LC/MS/MS method for determination of lornoxi cam in human plasma and investigate pharmacokinetics of single dose of lornox icam 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-C 8 column. The mobi le phase consisted of methanol-water-formic acid (80∶20∶0 5) at a flow-ra te of 0 7 mL·min -1 . A Finnigan TSQ tandem mass spectrometer equipped with atmospheric pressure chemical ionization source was used as detector and o perated in the positive ion mode. Selected reaction monitoring (SRM) using the p recursor → 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 μg·L -1 . The limit of quantitation was 2 0 μg·L -1 . The method was suc cessfully used in the pharmacokinetic study for lornoxicam. The main parameters obtained after an oral dose of 8 mg lornoxicam to 18 Chinese male volunteers wer e as follows: the value of T 1/2 was (4 7±1 1) h, AUC 0-∞ was found to be (5 5±2 4) mg·h·L -1 . However, T 1/2 of 105 h and AUC 0-∞ of 189 5 mg·h·L -1 were obtained for another volun teer. Conclusion The method is proved to be suitable for clinical investigation of lornoxicam pha rmacokinetics, which offers advantages of specificity, speed, and higher sensiti vity over the previously reported methods.

关 键 词：氯诺昔康 血药浓度 液相色谱-质谱-质谱联用技术 非甾体类抗炎药 药物代谢动力学 

分 类 号：R971.1[医药卫生—药品] R969.1[医药卫生—药学]