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目的用HPLC-MS/MS法手性拆分氨氯地平,高通量分析氨氯地平对映体在健康人体内的立体选择性药代动力学。方法 12例健康男性受试者单次口服氨氯地平5 mg,用Oasis HLB 96孔固相萃取板提取氨氯地平,以氯氮为内标,用CHIRAL-AGP柱(4.0 mm×150 mm,5μm)进行手性对映体分离,流动相10mmol·L~(-1)乙酸铵缓冲液(pH4.38)-异丙醇(98∶2)。结果 S-(-)-氨氯地平和R-(+)-氨氯地平主要药代动力学参数:C_(max)分别为(3.19±0.50),(1.99±0.27)ng·mL~(-1);t_(max)分别为(6.17±0.57),(6.80±1.60)h;t_(1/2)分别为(38.10±4.75),(32.54±6.58)h;AUC_(0-∞)分别为(195.48±39.20),(140.45±18.00)ng·mL~(-1)·h。结论本方法操作简便快速,灵敏度高,精密度好,可实现受试药人体手性药代动力学的高通量分析;S-(-)-氨氯地平对映体和R-(+)-氨氯地平对映体在健康男性人体内存在立体选择性差异。
Aim To analyze the stereoselective pharmacokinetics of amlodipine enantiomers in healthy volunteers by chiral resolution of amlodipine by HPLC-MS / MS. Methods Twelve healthy male subjects were given single oral amlodipine 5 mg orally, and amlodipine was extracted with Oasis HLB 96-well solid-phase extraction plate. The internal standard was treated with chlordiazepoxide (HPLC) column (4.0 mm × 150 mm , 5μm). The mobile phase consisted of 10mmol·L -1 ammonium acetate buffer (pH4.38) -isopropanol (98: 2). Results The main pharmacokinetic parameters of S - (-) - amlodipine and R - (+) - amlodipine were (3.19 ± 0.50) and (1.99 ± 0.27) ng · mL ~ (- 1 and t_ (max) were (6.17 ± 0.57) and (6.80 ± 1.60) h respectively; t 1/2 was 38.10 ± 4.75 and 32.54 ± 6.58 h respectively; AUC 0 -∞ (195.48 ± 39.20), (140.45 ± 18.00) ng · mL -1 (-1) h. Conclusion The method is simple and rapid in operation with high sensitivity and good precision, and can achieve high-throughput analysis of the chiral pharmacokinetics of the test drug. The enantiomers of S - (-) - amlodipine and R - Stereoselective Separation of Amlodipine Enantiomers in Healthy Male.