目的:建立同时测定血清中氯氮平及其代谢物去甲氯氮平的浓度的高效液相色谱法(HPLC)。方法:血清乙醚提取浓集后进样,采用反相C₁₈柱,以甲醇-水-四甲乙二胺-冰醋酸(68∶32∶0.40∶0.35)为流动相,地西泮为内标,在波长254nm处测定。结果:氯氮平和去甲氯氮平的线性范围分别为50ng·ml^-1～1500ng·ml^-1和20ng·ml^-1～1000ng·ml^-1,两者平均回收率均大于85%,日内和日间误差小于4%。结论:本法简便、灵敏、准确,适用于治疗药物监测和药动学研究。

OBJECTIVE: To simultaneously determine clozapine and its metabolite norclozapine in seurm concentration by HPLC. METHODS: Diazepam was selected as an internal standard HPLC with a UV detector and C₁₈ was used. Serum sample (0.5 ml) was extracted with 5 ml ether absolute after alkalized with 0.1 mol·L^-1 NaOH (100 μl). The organic layer was evaporated to dryness under N₂ stream in 50 ℃ water bath. The residue was dissolved in 100 ml mobile phase and 20 μl was injected. The mobile phase included methanol and water. RESULTS: The linearity of clozapine and norclozapine was 50 ng·ml^-1～1 500 ng·ml^-1 and 20 ng·ml^-1～1 000 ng·ml^-1, respectively. The RSD of inter-day and intra-day in two substances was less than 4%. The extraction recovery was 86%～92%. The detection limits in serum was 5 ng·ml^-1 for clozapine and 2 ng·ml^-1for norclozapine. CONCLUSION: The method was accurate and sensitive, and suitable for TDM and pharmacokinetic study of clozapine.