摘要
目的:建立同时测定人血浆中氯氮平及去甲氯氮平浓度的阳离子色谱柱-HPLC法。方法:用强阳离子交换色谱柱-HPLC测定人血浆中氯氮平及去甲氯氮平浓度,色谱柱为强阳离子交换色谱柱(4.6 mm×100 mm,5μm),流动相为乙腈-0.01 mol·L-1磷酸铵溶液(pH 5.1)(60∶40),流速为1.2 mL·min-1,紫外检测波长为257 nm,以AF2672为内标,含氯氮平及去甲氯氮平的血样经C8固相小柱萃取后进样。结果:阳离子色谱柱-HPLC测得氯氮平、去甲氯氮平的色谱峰峰形对称、无内外源性物质干扰,检测结果稳定、可靠、重复性好;通过改变流动相pH易于调整各化合物保留时间,同时去除空白血浆干扰;固相萃取前处理简单、省时且萃取回收率较高。氯氮平及去甲氯氮平浓度在50.4～990 ng·mL-1范围内线性关系良好;氯氮平及去甲氯氮平低(50.4 ng·mL-1)、中(396 ng·mL-1)、高(990 ng·mL-1)3个浓度的萃取回收率均大于91%,日内和日间RSD均小于4%(n=5)。结论:阳离子色谱柱-HPLC法测定人血浆中氯氮平及去甲氯氮平浓度,色谱峰峰形对称,保留时间适宜且无杂质干扰,适用于临床氯氮平及去甲氯氮平血药浓度监测和药动学研究。
Objective：To establish a method for determination of clozapine and N - desmethylclozapine in human plasma by strong cation exchange column - HPLC （ SCX - HPLC ）. Methods： Clozapine and N - desmethylclozapine were separated on a SCX column using a mobile phase comprised of acetonitrile -0.01 mol . L-1 ammonium phos- phate（pH 5.1 ） （60： 40） with the flow rate of 1.2 mL.min-l. The UV detector was set at 257nm and AF2672 was used as the internal standard. Clozapine and N - desmethylelozapine were extracted by Cs solid extraction column. Results： The SCX - HPLC method could achieve a symmetrical peak for elozapine and N - desmethylclozapine, with no interference from endogenous and exogenous substances, by which the detection result was stable, reliable and re- producible. The retention time of analytes and plasma interference were adjusted by changing the pH of mobile phase;the solid phase extraction method is simple, time - saving with high efficiency of extraction. The calibration curve showed good linearity in the range of 50.4 - 990 ng. mL- 1 for clozapine and N - desmethylclozapine. The ab- solute recoveries in low,middle and high concentration were both more than 91%, and the intra -day and inter- day variations（RSDs） were both less than 4% （n = 5 ）. Conclusion ：The established method was used for the deter- mination of clozapine and N - desmethylclozapine in human plasma, the chromatographic peak was symmetrical, the retention time was appropriate without interference. It was suitable for the plasma drug concentration monitoring and pharmacokinetic study of clozapine and N - desmethylclozapine.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2013年第1期44-49,共6页
Chinese Journal of Pharmaceutical Analysis
