摘要
建立了测定人血清中氯氮平及其去甲基代谢物的柱前衍生化气相色谱－质谱选择离子监测的分析方法。以三氟乙酸酐作酰化剂，对衍生化条件和样品预处理方法实施了优化。氯氮平和去甲氯氮平的线性范围为１～１２８μｇ／Ｌ，最低检测浓度：氯氮平为０．１μｇ／Ｌ，去甲氯氮平为０．２μｇ／Ｌ，两者的回收率均大于８３％，相对标准偏差都小于１０％。将所建立的方法应用于服用细胞色素氧化酶Ｐ４５０１Ａ２抑制剂前后低剂量氯氮平的药代动力学自身对照试验中，结果显示氯氮平的代谢水平明显受Ｐ４５０１Ａ２活性的影响。
This article reports a highly sensitive method specific for determination of clozapine(CLP) and its N demethylated metabolite (DCLP) in serum by gas chromatography mass spectrometry with selected ion monitoring. A 0 5mL serum was alkalized with 0 5mL 1 0mol/L sodium hydroxide and was extracted with 5mL ether, then the organic phase was transferred to another tube containing 1mL 0 1mol/L hydrochloric acid. After being shaken and centrifuged, the organic phase was discarded,and 10μL 100μg/L diazepam(DAP) was added to the water phase as internal standard, then 0 5mL 1 0mol/L sodium hydroxide and 5mL ether were added. The extract was evaporated to dryness and then was acylated with 50μL trifluoroacetic anhydride under 50℃ for 45min. The excess of the reagent was evaporated and the residue was dissloved in 20μL acetone. Take 2μL for gas chromatography mass spectrometry analysis. Chromatographic conditions were:column DB 1(30m×0 25mm×0 25μm),injector 260℃, interface 250℃,column oven with temperature program: 120℃(1min)40℃/min250℃(0 5min)20℃/min290℃(3min) Helium carrier gas flow rate was 1 8mL/min. The mass spectrometer was adjustd to record the ion m/z 352 for CLP and DCLP, and m/z 256 for DAP in quantitation. The minimum detection limits were 0 1μg/L for CLP and 0 2μg/L for DCLP. The standard curves of CLP and DCLP were linear between 1 128μg/L ( r CLP =0 998, r DCLP =0 999). Recoveries of two substances were better than 83%, and the RSD values were less than 10%. This method has been successfully used in clinical pharmacokinetic study of CLP before and after CYP1A2 inhibitor used. The results indicate that the metabolism of clozapine is strongly affected by CYP1A2 activity.
出处
《色谱》
CAS
CSCD
北大核心
1998年第4期317-320,共4页
Chinese Journal of Chromatography
关键词
氯氮平
去甲氯氮平
代谢物
测定
色质联用
gas chromatography mass spectrometry, clozapine, desmethylclozapine, derivatization
