反相高效液相层析法测定血浆中氯雷他定浓度及药动学研究

Determination of plasma loratadine concentration with RP-HPLC and its pharmacokinetic study

目的:建立测定血浆中氯雷他定浓度的反相高效液相层析方法,并对其在人体内的药动学进行研究.方法:血浆中氯雷他定用正己烷-甲基叔丁基醚(1:1)作液-液萃取挥干后,加流动相进样分析.反相高效液相层析方法采用Hypersil-BDS层析柱,流动相为乙腈-水(65:35,磷酸调pH 3.8),流速1.0 ml/min;紫外检测波长为248 nm.结果:氯雷他定在0.506 0～50.60 ng/ml血浆浓度范围内线性良好(r=0.999 5),平均相对回收率＞95.0%,日间和日内RSD＜15.0%.主要药代动力学参数:t1/2为(1.57±0.18)h;MRT为(2.46±0.19)h;Cl/F为(583.7±215.0)L/h cmax为(37.40±8.92)ng/ml;tmax为(1.0±0.20)h;AUC0～8 h为(73.24±21.30)ng·h/ml AUC0～∞为(75.57±21.70)ng·h/ml.结论:该方法操作方便,结果准确,可用于血浆中氯雷他定药代动力学研究.

Objective : To establish a RP-HPLC method for the determination and pharmacokinetic study of loratadine in Chinese healthy volunteers. Methods; Chrornatography was performed on a Hypersil-BDS with acetonitrile-water (65 : 35, pH was adjusted to 3. 8 with H3PO4) as mobile phase. The flow rate was 1. 0 ml/min and the UV wavelength was set at 248 nm. Results: Good linearity was found within 0. 506 0-50. 60 ng/ml of loratadine in human plasma(r = 0. 999 5). The mean relative recovery rate was more than 95% ; intra-day and inter-day RSD were less than 15. 0%. The limit of detection was 0. 506 ng/ml. The main pharmacokinetic parameters were as follows:t12 was (1. 57 ± 0. 18) h;MRT was (2. 46±0. 19) h;Cl/ F was (583. 7±215. 0) L/h;cmax, was (37. 40±8. 92) ng/ml;tmax was (1. 0±0. 20) h;AUC0-8h was (73. 24±21. 30) ng · h/ ml;.AUC/C0-∞ was (75. 57±21. 70) ng · h/ml. Conclusion: Our method has a good selectivity and sensitivity and can be used for further clinical pharmacokinetic study of loratadine.