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目的建立测定人血中左旋舒必利浓度的高效液相色谱串联质谱电喷雾检测法(LC-MS/MS)。方法血浆样品用乙酸乙酯-二氯甲烷(V∶V=4∶1)提取,色谱柱为Agilient TC-C18柱,流动相为甲醇-乙腈-5 mmol·L-1醋酸铵(含体积分数为2%的甲酸)(V∶V∶V=85∶10∶5),流速为0.8 m L·min-1;质谱:采用多反应检测模式,API2000电喷雾离子源。结果左旋舒必利线性为1~600μg·L-1;定量下限为1μg·L-1;日间日内精密度(RSD)均不大于14.8%。准确度(RE):-6.8%~9.5%。健康受试者单剂量口服左旋舒必利25、50和100 mg及多剂量口服50 mg后,受试制剂的主要药物动力学参数为:tmax分别为(3.67±0.65)、(3.75±1.14)、(3.33±0.49)和(2.75±1.14)h,ρmax分别为(40.28±11.13)、(74.75±16.21)、(179.08±35.78)和(131.83±43.18)μg·L-1,t1/2分别为(13.19±3.69)、(13.21±4.71)、(11.74±2.45)、(18.59±10.81)h,AUC0-t分别为(473.6±125.0)、(841.20±203.67)、(1687.62±373.98)和(1848.17±610.65)μg·h·L-1。单剂量口服左旋舒必利后,在25~100 mg剂量内,AUC0-t、ρmax呈线性动力学特征趋势,多剂量给药7 d,左旋舒必利在体内有一定蓄积。各剂量组的药物动力学参数在男女性别间无显著性差异。结论该法适合于左旋舒必利的人体药物动力学研究。
Objective To establish a liquid chromatography tandem mass spectrometry (LC-MS / MS) method for the determination of levosulpiride in human blood. Methods The plasma samples were extracted with ethyl acetate-dichloromethane (V:V = 4: 1). The column was Agilient TC-C18 and the mobile phase consisted of methanol-acetonitrile 5 mmol·L -1 ammonium acetate 2% formic acid) (V: V: V = 85: 10: 5) at a flow rate of 0.8 m L · min-1. MS: API2000 electrospray ionization source with multiple reaction detection mode. Results The linearity of levosulpiride was 1 ~ 600μg · L-1. The lower limit of quantification was 1μg · L-1. The daily intra-day precision (RSD) was no more than 14.8%. Accuracy (RE): - 6.8% ~ 9.5%. The main pharmacokinetic parameters of healthy subjects were as follows: tmax was (3.67 ± 0.65), (3.75 ± 1.14), (3.75 ± 1.14), ( 3.33 ± 0.49 and 2.75 ± 1.14 h, respectively, and the values of ρmax were (40.28 ± 11.13), (74.75 ± 16.21), (179.08 ± 35.78) and (131.83 ± 43.18) μg · L -1, respectively AUC0-t were (473.6 ± 125.0), (841.20 ± 203.67), (1687.62 ± 373.98), and (1848.17 ± 13.7 ± 3.69), (13.21 ± 4.71), (11.74 ± 2.45) and (18.59 ± 10.81) 610.65) μg · h · L-1. After a single dose of oral levosulpiride, AUC0-t and ρmax showed a linear kinetic trend in the dose range of 25-100 mg. After multi-dose administration for 7 days, levosulpiride accumulated in the body. Pharmacokinetic parameters of each dose group did not differ significantly between men and women. Conclusion This method is suitable for the study of human pharmacokinetics of levosulpiride.