HPLC法测定氯氮平和三环类抗抑郁药及其去甲基代谢产物的血清浓度  

DETERMINATION OF CLOZAPINE, TRICYCLIC ANTIDEPRESSANTS AND THEIR DESMETHYL METABOLITES IN SERUM BY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY

作　　者：李文标[1] 秦英绂[1] 翟屹民[1] 郭桂欣[1] 徐敏洁[1] 

机构地区：[1]首都医科大学附属北京安定医院临床精神药理实验室,北京100088

出　　处：《中国临床药理学杂志》1999年第5期369-373,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：本文报道了一种反相高效液相色谱法 ,可同时测定氯氮平、去甲氯氮平、多塞平、去甲多塞平、阿米替林和去甲替林的血清浓度。本法选用IntersilODS -3柱为固定相 ,甲醇、乙腈和正丁胺 -冰醋酸缓冲液的混合液(5:35:60)为流动相 ,去甲米帕明为内标 ,紫外检测波长254nm。1ml待测血清加内标后 ,经0.5ml1mol·L -1NaOH碱化 ,加重蒸乙醚4ml提取 ,再用1ml0.2mol·L -1HCl反提取 ,最后经1ml2mol·L-1 NaOH碱化后用4ml重蒸乙醚提取 ,氮气吹干 ,流动相重组后进样分析。本法对各被测物的最低检测限在3～10ng之间 ,最低检测浓度在6～16μg·L-1 之间 ,提取回收率在65 %～81 %之间 ,批内和批间变异系数均小于10 % ,线性范围至少在25～800μg·L-1 之间。本法不受常用精神药物及其它药物的干扰 ,并已用于临床治疗药物监测工作和研究工作。A reversed-phase HPLC method was reported for the simultaneous determination of clozapine, norclozapine, doxepin, nordoxepin, amitriptyline and nortriptyline in serum. An intersil ODS-3 column was used as the solid phase. The mobile phase was composed of methanol, acetonitrile and n-butylamine-acetic acid buffer (5:35:60). The separated drugs were detected at UV 254 nm. Desipramine was used as the internal standard. After adding the internal standard, 1 ml of patient serum was basified with 0.5 ml of 1mol·L-1 sodium hydroxide solution. 4 ml distilled diethyl ether was used to extract the drugs. Adding 1 ml of 0.2 mol·L-1 hydrochloric acid to the organic phase and extracted, the aqueous phase was re-basified with 1ml of 2 mol·L-1 sodium hydroxide solution and re-extracted with 4 ml distilled diethyl ether. This organic phase was evaporated to dryness by a stream of nitrogen. The residue was reconstituted with 50 μl mobile phase and injected into the HPLC system for analysis. The lowest detection limits of the drugs assayed are 3～10 ng. The level of determination was 6～16 μg·L-1 in serum. The extraction recoveries were 65%～81%. The interassay and intraassay variance was less than 10%. The standard curves were linear at list within the range of 25～800 μg·L-1 of all these drugs. This assay was not interfered by routine psychotropic drugs and other drugs. It has been used for the therapeutic drug monitoring of these drugs and research works.

关 键 词：氯氮平 三环类抗抑郁药 去甲基代谢物 血药浓度 

分 类 号：R971.43[医药卫生—药品] R969.1[医药卫生—药学]