UPLC-MS/MS方法测定盐酸哌替啶原料及注射液中的神经毒性杂质1-甲基-4-苯基-1,2,3,6-四氢吡啶  

Determination of neurotoxicity impurity MPTP in pethidine hydrochloride API and injection by UPLC-MS/MS

作　　者：沈雨婷 马迅[1] 南楠[1] 

机构地区：[1]中国食品药品检定研究院,北京100050

出　　处：《药物分析杂志》2016年第5期911-917,共7页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立UPLC-MS/MS方法,定量分析盐酸哌替啶原料及注射液中的神经毒性杂质——1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)。方法:采用ACQUITY CSH Phenyl-Hexyl(2.1 mm×100 mm,1.7 m)色谱柱进行色谱分离,流动相位0.1%甲酸水-乙腈,梯度洗脱;以三重四极杆作为检测器,采用多反应监测(MRM)扫描方式,选择母离子(m/z 174)→子离子(m/z 44)作为MRM定量离子对。用该方法检测盐酸哌替啶原料药及其注射液中MPTP,MPTP的含量按峰面积以外标法计算。结果:MPTP质量浓度在0.25～201.4 ng·m L^(-1)范围内线性关系良好(r=0.999 6);平均加样回收率(n=9)为102.5%,RSD为1.5%;供试品溶液在24 h内的稳定性良好(RSD=1.6%);MPTP的定量限1.93×10^(-2) ng·mL^(-1),检出限为0.58×10-2 ng·m L^(-1);3批原料药中MPTP含量为175～185 ng·g^(-1),10批注射液中MPTP含量为6.3～33.2ng·mL^(-1)。结论:本方法适用于盐酸哌替啶原料药及注射液中MPTP的含量测定。Objective：To establish a UPLC-MS/MS method for reliable quantitative analysis of 1-methyl-4-pheyl-1,2,3,6-tetrahydropyridine（MPTP） in pethidine hydrochloride active pharmaceutical ingredient（API） and injection.Methods：An ACQUITY CSH Phenyl-Hexyl（2.1 mm×100 mm,1.7 m） column was adopted to achieve chromatographic separation with gradient elution.T mobile phase consisted of water containing 0.1% formic acid and acetonitrile.The triple quadrupole is operated in the multi reaction monitoring（MRM） mode,selecting the m/z 174 → m/z 44 as the quantitative ion pair.Pethidine hydrochloride API and injection from pharmaceutical companies was determined by the method,and the content computation was performed with external standard carve method.Results：The linear range of MPTP was 0.25-201.4 ng·m L^-1 with the correlation coefficient（r=0.999 6）.The average recovery（n=9） was 102.5%,RSD=1.5%.The sample solution was stable within 24 h（RSD=1.6%）.The limit of quantitation of MPTP was 1.93×10（-2） ng·m L^-1 and the limit of detection was 0.58×10-2 ng·m L^-1.The contents of MPTP in 3 API samples were 175-185 ng·g^-1,and the contents of MPTP in 10 injection samples were 6.3-33.2 ng·m L^-1.Conclusion：The established method can be applied to the content determination of MPTP in pethidine hydrochloride API and injection.

关 键 词：1-甲基-4-苯基-1 2 3 6-四氢吡啶(MPTP) 神经毒性杂质 盐酸哌替啶 有关物质测定 超高效液相色谱串联质谱 多反应监测 

分 类 号：R917[医药卫生—药物分析学]