Rapid Simultaneous Determination of Paracetamol, Amantadine Hydrochloride, Caffeine and Chlorpheniramine Maleate in Human Plasma by Liquid Chromatography/Tandem Mass Spectrometry
Rapid Simultaneous Determination of Paracetamol, Amantadine Hydrochloride, Caffeine and Chlorpheniramine Maleate in Human Plasma by Liquid Chromatography/Tandem Mass Spectrometry
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DOI：
10.1055/s-0031-1296369
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发表时间：
2009-01-01
影响因子：
--
通讯作者：
Chen, Yun
中科院分区：
文献类型：
--
作者：
Feng, Shudan;Tian, Yuan;Chen, Yun
一种快速、简便、灵敏的高效液相色谱-正离子电喷雾串联质谱首次开发并验证了HPLC-ESI-MS/MS同时测定对乙酰氨基酚（PAR，CAS 103-90-2），盐酸金刚烷胺使用盐酸曲马多（TMH，CAS 22204-88-2）作为内标物（IS），测定人血浆中盐酸曲马多（ATH，CAS 665-66-7）、咖啡因（CAF，CAS 58-08-2）和马来酸氯苯那敏（CPM，CAS 113-92-8）的浓度。在甲醇诱导的蛋白质沉淀后，使用由甲醇：水（0.5%甲酸）= 20：80（v/v）组成的移动的相在市售柱（150 mm x 2.1 mm I.D.，5 μ m），并通过电喷雾电离串联质谱法以选择反应监测（SRM）模式进行分析，PAR的前体至产物离子跃迁m/z为152.3 -> 110.2，ATH为152.3 -> 135.3，CAF为195.1 -> 138.3，CPM为275.2 -> 230.3，TMH为264.2 -> 58.2。PAR在0.2-20 μ g/mL、ATH和CAF在20-2000 ng/mL、CPM在0.1-10 ng/mL范围内与峰面积呈良好的线性关系（r（2）> 0.99），精密度和准确度均较好。批内和批间精密度的相对标准偏差（RSD）小于15%。PAR、ATH、CAT和CPM的定量下限（LLOQ）分别为0.2 μ g/mL、20 ng/mL、20 ng/mL和0.1 ng/mL。该方法已成功地应用于盐酸金刚烷胺对乙酰氨基酚片在中国健康男性志愿者体内的药代动力学研究，具有良好的精密度和灵敏度。
A rapid, simple and sensitive high performance liquid chromatography with positive ion electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was first developed and validated to simultaneously determine paracetamol (PAR, CAS 103-90-2), amantadine hydrochloride (ATH, CAS 665-66-7), caffeine (CAF, CAS 58-08-2) and chlorpheniramine maleate (CPM, CAS 113-92-8) in human plasma using tramadol hydrochloride (TMH, CAS 22204-88-2) as internal standard (IS). Following methanol-induced protein precipitation, the analytes were separated using a mobile phase comprised of methanol: water (0.5% formic acid) = 20:80 (v/v) on a commercially available column (150 mm x 2.1 mm I.D., 5 mu m) and analyzed by electrospray ionization tandem mass spectrometry in the selected reaction monitoring (SRM) mode with the precursor to product ion transitions m/z 152.3 -> 110.2 for PAR, 152.3 -> 135.3 for ATH, 195.1 -> 138.3 for CAF, 275.2 -> 230.3 for CPM and 264.2 -> 58.2 for TMH. The standard curves were linear (r(2) > 0.99) over the concentration range of 0.2-20 mu g/mL for PAR, 20-2000 ng/mL for ATH and CAF, 0.1-10 ng/mL for CPM and had good accuracy and precision, respectively. The within- and between-batch precisions were less than 15% in terms of relative standard deviation (RSD). The lower limit of quantitation (LLOQ) were 0.2 mu g/mL, 20 ng/mL, 20 ng/mL and 0.1 ng/mL for PAR, ATH, CAT and CPM, respectively. The described method has been successfully applied to study the pharmacokinetics of paracetamol-amantadine hydrochloride tablets in Chinese healthy male volunteers with great precision and sensitivity.