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目的采用LC-MS/MS测定人血浆中普瑞巴林的药物浓度,并应用于健康受试者体内药物动力学研究。方法以加巴喷丁为内标,采用Waters Symmetry C_(18)(3.9 mm×150 mm,5μm)色谱柱,流动相为乙腈-5 mmol·L~(-1)醋酸铵水溶液(含0.3%甲酸)=8∶92(V/V),流速为1.0 m L·min~(-1),每个样品的分析时间为6.0 min,样品经大气压力化学离子源正离子化后,通过三重四极杆串联质谱仪,在多反应监测模式下测定普瑞巴林(m/z 160.1→142.1)和内标加巴喷丁(m/z 172.1→154.1)的浓度。血浆样品前处理采用甲醇沉淀蛋白。结果普瑞巴林的血浆浓度在30.00~5 000 ng·m L~(-1)内线性良好,定量下限为30.00ng·m L~(-1),批内、批间精密度(RSD)均在2.0%~6.2%以内,相对偏差(RE)在~(-1)0.5%~3.0%以内。血浆样品室温(25℃)放置6 h,反复冻融(-30℃)3次及冰冻(-30℃)保存27 d的情况下均稳定。真正样品再分析(ISR)实验准确度符合要求。结论该分析方法简便、特异性高、灵敏度高,可用于受试者空腹口服75 mg普瑞巴林胶囊后血浆样品中普瑞巴林的药动学研究。
Objective To determine the concentration of pregabalin in human plasma by LC-MS / MS and to study the pharmacokinetics of pregabalin in human plasma. Methods The gabapentin was used as internal standard. The mobile phase was acetonitrile-5 mmol·L -1 ammonium acetate solution (containing 0.3% formic acid) with a Waters Symmetry C 18 (3.9 mm × 150 mm, 5 μm) The flow rate was 1.0 m L · min ~ (-1) at 8:92 (V / V) and the analysis time was 6.0 min for each sample. The samples were ionized by atmospheric pressure chemical ion source and tandem Mass spectrometer, the concentrations of pregabalin (m / z 160.1 → 142.1) and the internal standard gabapentin (m / z 172.1 → 154.1) were determined in a multiplex reaction monitoring mode. Plasma samples were pre-treated with methanol to precipitate the protein. Results The plasma concentration of pregabalin was linear in the range of 30.00-5 000 ng · m L -1 with a lower limit of quantitation of 30.00 ng · m L -1. Intra- and inter-batch precision (RSD) Within 2.0% ~ 6.2%, the relative deviation (RE) is within ~ (-1) 0.5% ~ 3.0%. Plasma samples were stable at room temperature (25 ° C) for 6 h, repeatedly frozen and thawed (-30 ° C) for 3 times and frozen (-30 ° C) for 27 days. True sample reanalysis (ISR) experiment accuracy meets requirements. Conclusion The method is simple, specific and sensitive. It can be used to study the pharmacokinetics of pregabalin in plasma samples of 75 mg oral pregabalin capsules.