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目的:建立灵敏的氯雷他定血浓度测定方法,评价氯雷他定的药代动力学特点。方法:固定相ORBAX Eclipse XDB-C8(5μm,150 mm×4.6 mm),HP1100LC-MSD质谱检测器;流动相乙腈-0.1%醋酸和0.2%醋酸铵水溶液,流速1.0 ml.min-1。离子源:AP-ESI,正离子模式,雾化电压30 psi,保护气10 L.min-1N2,毛细管电压4 000 V,碎片电压为170 V。SIM离子采集方式,采集离子(m/z)氯雷他定383.2(M+H),内标罗哌卡因275.1(M+H)。结果:氯雷他定线性范围0.5~50 ng.ml-1,最低定量限为0.5 ng.ml-1。氯雷他定片(T1)、胶囊(T2)、开瑞坦(R)主要药代动力学参数t1/2为13.52±1.35,13.14±0.98,14.00±1.25 h;Tmax为1.24±0.06,1.18±0.12,1.18±0.12 h;Cmax为21.72±7.70,21.49±8.34,20.50±8.65 ng.ml-1;AUC0-48为137.24±47.87,139.65±45.69,134.19±49.03ng.h.ml-1,AUC0-∞为146.61±51.03,148.04±48.10,143.70±52.08 ng.h.ml-1。试验制剂氯雷他定片/胶囊相对生物利用度分别为(105.49±8.08)%和(102.90±10.02)%。结论:HPLC-MS法测定氯雷他定血浓度实用、可行,适用于常规治疗药物监测和氯雷他定药代动力学研究。试验制剂和参比制剂为生物等效制剂。
Objective: To establish a sensitive method for the determination of loratadine and evaluate the pharmacokinetics of loratadine. METHODS: The mobile phase consisted of ORBAX Eclipse XDB-C8 (5μm, 150 mm × 4.6 mm) and HP1100 LC-MSD detector. The mobile phase consisted of acetonitrile-0.1% acetic acid and 0.2% aqueous ammonium acetate solution at a flow rate of 1.0 ml.min-1. Ion source: AP-ESI, positive ion mode, atomization voltage of 30 psi, shield gas of 10 L.min-1N2, capillary voltage of 4 000 V and fragment voltage of 170 V. SIM ion acquisition mode, collecting ion (m / z) loratadine 383.2 (M + H), internal standard ropivacaine 275.1 (M + H). Results: Loratadine linear range of 0.5 ~ 50 ng.ml-1, the lowest limit of quantification of 0.5 ng.ml-1. The main pharmacokinetic parameters t1 / 2 of loratadine tablets (T1), capsules (T2) and kaitirtan (R) were 13.52 ± 1.35, 13.14 ± 0.98 and 14.00 ± 1.25 h; Tmax was 1.24 ± 0.06 and 1.18 ± 0.12,1.18 ± 0.12 h; Cmax 21.72 ± 7.70,21.49 ± 8.34,20.50 ± 8.65 ng.ml-1; AUC0-48 was 137.24 ± 47.87,139.65 ± 45.69,134.19 ± 49.03 ng.h.ml-1, AUC0 -∞ was 146.61 ± 51.03, 148.04 ± 48.10, 143.7 ± 52.08 ng.h.ml-1. The relative bioavailability of loratadine tablet / capsule was (105.49 ± 8.08)% and (102.90 ± 10.02)%, respectively. Conclusion: HPLC-MS method for the determination of loratadine blood concentration is practical and feasible, suitable for routine treatment drug monitoring and loratadine pharmacokinetic studies. The test and reference formulations are bioequivalent formulations.