RpHplc法测定全血、血浆和红细胞中氯氮平及2种主要代谢物
翟屹民，李文标，王传跃，郭桂欣，张 军
(首都医科大学附属北京安定医院临床精神药理室，北京 100088)
[摘要]目的：建立一种测定全血、血浆和红细胞中氯氮平(CZP)、N去甲基氯氮平(NCZP)和氯氮平N氧化物(CZPNO)浓度的RPHPLC法。方法：标本用乙酸乙酯提取后再经0.1mol·L-1盐酸反提取，以利培酮为内标，流动相为甲醇乙腈水(16.0∶36.5∶47.5)，色谱柱为InertsilODS3柱，柱温为40℃，检测波长为254nm，流速为0.9mL·min-1。结果：全血、血浆和红细胞中CZP和NCZP的最低检测浓度均为7μg·L-1；血浆中CZPNO的最低检测浓度为13μg·L-1，全血和红细胞中为14μg·L-1。全血、血浆和红细胞中CZP和NCZP的绝对回收率均为85%～95%，血浆中CZPNO的绝对回收率>82%，全血和红细胞中CZPNO的绝对回收率约为70%。日内和日间RSD均小于7%。结论：本法操作简便，灵敏度高，重复性好，适合于临床检测。
, 百拇医药
[关键词]氯氮平；反相高效液相色谱法；全血；血浆；红细胞
[中图分类号]*"R971.41[文献标识码]*"A[文章编号]*"1003-3734(2002)02-0141-04
RPHPLC determination of clozapine and its two major metabolites in whole blood,plasma and red blood cells
ZHAI Yimin, LI Wenbiao, WANG Chuanyue, GUO Guixin,ZHANG Jun
(Laboratory of Clinical Psychopharmacology,Beijing Anding Hospital Affiliated to Capital University of Medical Sciences，Beijing 100088,China)
, http://www.100md.com
[Abstract]Objective:To establish a RPHPLC method for the simultaneous determination of clozapine(CZP) and its two major metabolites Ndemethylclozapine(NCZP) and clozapine Noxide (CZPNO) in human whole blood,plasma and red blood cells.Methods:Risperidone was used as internal standard. Blood samples were extracted with ethyl acetate and further purified with 0.1mol·L-1 hydrochloric acid.The compounds were separated on an InertsilODS3 column maintained at the temperature of 40℃and were monitored by ultraviolet detector at 254nm.The mobile phase was methanolacetonitrilewater(16.0∶36.5∶47.5) and the flow rate was 0.9ml·min-1.Results:When 0.5mL blood sample was used for the analysis, the lowest limit of detected concentration was both 7μg·L-1 for CZP and NCZP in human whole bolld,plasma and red blood cells,and 13μg·L-1 for CZPNO in plasma and 14μg·L-1 for CZPNO in human whole blood and red blood cells.The absolute recovery was both 85%～95% for CZP and NCZP in human whole blood,plasma and red blood cells,and over 82% for CZPNO in plasma,and 70% for CZPNO in human whole blood and red blood cells. The withinday and betweenday variance was proved to be less than 7%.Conclusion:This method was validated with respect to simplicity,accuracy, sensitivity and precision.
, http://www.100md.com
[Key words]clozapine;RPHPLC;whole blood;plasma;red blood cell
[作者简介]翟屹民(1964-)，女，副主任技师。主要从事精神科药物治疗药物监测。联系电话：(010)82085465。
[参考文献]
[1]Perry PJ,Miller DD,Amdt SV,et al.Clozapine and norclozapine plasma concentration concentrations and clinical response of treatmentrefractory schizophrenic patients[J].Am J Psychiatry,1991,148(2)∶231-235.
[2]司天梅，舒良.氯氮平的药代动力学及血药浓度与临床疗效的关系[J].中国临床药理学杂志，1996，12(3)∶178-183.
, 百拇医药
[3]汤宜朗.氯氮平治疗难治性精神分裂的效能及疗效相关因素的筛选与评估[J].中华精神科杂志,1997，30(3)∶162-166.
[4]Kaladjian A,Bery B,Deturmmeny E，et al.Clozapine monitoring:plasma or serum levels[J]?Ther Drug Monit，1999，21(3)∶327-329.
[5]Aymard N,Baldacci C,Leyris A,et al.Neurolepticresistant schizophrenic patients treated by clozapine:clinical evolution, plasma and red blood cell,clozapine, Ndemethylclozapine[J].Therapie,1997，52(3)∶227-232.
, 百拇医药
[6]Lovdahl MJ,Perry PJ,Miller DD.The assay of clozapine and Ndemethylclozapine in human plasma by highperformance liquid chromatography[J].Ther Drug Monit,1991，13(1)∶69-72.
[7]Guitton C,Kinowski JM,Aznar R,et al.Determination of clozapine and its major metabolites in human plasma and red blood cells by highperformance liquid chromatography with ultraviolet absorbance detection[J].J Chromatogr B，1997，690∶211-222.
[8]翟屹民，秦英绂，李文标，等. 高效液相色谱法同时测定血清中氯氮平及N去甲基氯氮平浓度[J].中国医院药学杂志，1997，17(增刊)∶10-12.
[9]殷金龙，顾牛范，林治光，等.用HPLC测定血中氯氮平及N去甲基代谢物[J].上海精神医学，1990，2(1)∶24-26.
(收稿日期：2001-12-24)
, http://www.100md.com
(首都医科大学附属北京安定医院临床精神药理室，北京 100088)
[摘要]目的：建立一种测定全血、血浆和红细胞中氯氮平(CZP)、N去甲基氯氮平(NCZP)和氯氮平N氧化物(CZPNO)浓度的RPHPLC法。方法：标本用乙酸乙酯提取后再经0.1mol·L-1盐酸反提取，以利培酮为内标，流动相为甲醇乙腈水(16.0∶36.5∶47.5)，色谱柱为InertsilODS3柱，柱温为40℃，检测波长为254nm，流速为0.9mL·min-1。结果：全血、血浆和红细胞中CZP和NCZP的最低检测浓度均为7μg·L-1；血浆中CZPNO的最低检测浓度为13μg·L-1，全血和红细胞中为14μg·L-1。全血、血浆和红细胞中CZP和NCZP的绝对回收率均为85%～95%，血浆中CZPNO的绝对回收率>82%，全血和红细胞中CZPNO的绝对回收率约为70%。日内和日间RSD均小于7%。结论：本法操作简便，灵敏度高，重复性好，适合于临床检测。
, 百拇医药
[关键词]氯氮平；反相高效液相色谱法；全血；血浆；红细胞
[中图分类号]*"R971.41[文献标识码]*"A[文章编号]*"1003-3734(2002)02-0141-04
RPHPLC determination of clozapine and its two major metabolites in whole blood,plasma and red blood cells
ZHAI Yimin, LI Wenbiao, WANG Chuanyue, GUO Guixin,ZHANG Jun
(Laboratory of Clinical Psychopharmacology,Beijing Anding Hospital Affiliated to Capital University of Medical Sciences，Beijing 100088,China)
, http://www.100md.com
[Abstract]Objective:To establish a RPHPLC method for the simultaneous determination of clozapine(CZP) and its two major metabolites Ndemethylclozapine(NCZP) and clozapine Noxide (CZPNO) in human whole blood,plasma and red blood cells.Methods:Risperidone was used as internal standard. Blood samples were extracted with ethyl acetate and further purified with 0.1mol·L-1 hydrochloric acid.The compounds were separated on an InertsilODS3 column maintained at the temperature of 40℃and were monitored by ultraviolet detector at 254nm.The mobile phase was methanolacetonitrilewater(16.0∶36.5∶47.5) and the flow rate was 0.9ml·min-1.Results:When 0.5mL blood sample was used for the analysis, the lowest limit of detected concentration was both 7μg·L-1 for CZP and NCZP in human whole bolld,plasma and red blood cells,and 13μg·L-1 for CZPNO in plasma and 14μg·L-1 for CZPNO in human whole blood and red blood cells.The absolute recovery was both 85%～95% for CZP and NCZP in human whole blood,plasma and red blood cells,and over 82% for CZPNO in plasma,and 70% for CZPNO in human whole blood and red blood cells. The withinday and betweenday variance was proved to be less than 7%.Conclusion:This method was validated with respect to simplicity,accuracy, sensitivity and precision.
, http://www.100md.com
[Key words]clozapine;RPHPLC;whole blood;plasma;red blood cell
[作者简介]翟屹民(1964-)，女，副主任技师。主要从事精神科药物治疗药物监测。联系电话：(010)82085465。
[参考文献]
[1]Perry PJ,Miller DD,Amdt SV,et al.Clozapine and norclozapine plasma concentration concentrations and clinical response of treatmentrefractory schizophrenic patients[J].Am J Psychiatry,1991,148(2)∶231-235.
[2]司天梅，舒良.氯氮平的药代动力学及血药浓度与临床疗效的关系[J].中国临床药理学杂志，1996，12(3)∶178-183.
, 百拇医药
[3]汤宜朗.氯氮平治疗难治性精神分裂的效能及疗效相关因素的筛选与评估[J].中华精神科杂志,1997，30(3)∶162-166.
[4]Kaladjian A,Bery B,Deturmmeny E，et al.Clozapine monitoring:plasma or serum levels[J]?Ther Drug Monit，1999，21(3)∶327-329.
[5]Aymard N,Baldacci C,Leyris A,et al.Neurolepticresistant schizophrenic patients treated by clozapine:clinical evolution, plasma and red blood cell,clozapine, Ndemethylclozapine[J].Therapie,1997，52(3)∶227-232.
, 百拇医药
[6]Lovdahl MJ,Perry PJ,Miller DD.The assay of clozapine and Ndemethylclozapine in human plasma by highperformance liquid chromatography[J].Ther Drug Monit,1991，13(1)∶69-72.
[7]Guitton C,Kinowski JM,Aznar R,et al.Determination of clozapine and its major metabolites in human plasma and red blood cells by highperformance liquid chromatography with ultraviolet absorbance detection[J].J Chromatogr B，1997，690∶211-222.
[8]翟屹民，秦英绂，李文标，等. 高效液相色谱法同时测定血清中氯氮平及N去甲基氯氮平浓度[J].中国医院药学杂志，1997，17(增刊)∶10-12.
[9]殷金龙，顾牛范，林治光，等.用HPLC测定血中氯氮平及N去甲基代谢物[J].上海精神医学，1990，2(1)∶24-26.
(收稿日期：2001-12-24)
, http://www.100md.com