安徽医药
安徽醫藥
안휘의약
ANHUI MEDICAL AND PHARMACEUTICAL JOURNAL
2015年
7期
1260-1263
,共4页
朱冬春%程钢%孙旭群%苏涌%吴娟%夏泉%许杜娟
硃鼕春%程鋼%孫旭群%囌湧%吳娟%夏泉%許杜娟
주동춘%정강%손욱군%소용%오연%하천%허두연
细胞色素 P450%高效液相色谱法%氯唑沙宗%甲苯磺丁脲%咪达唑仑
細胞色素 P450%高效液相色譜法%氯唑沙宗%甲苯磺丁脲%咪達唑崙
세포색소 P450%고효액상색보법%록서사종%갑분광정뇨%미체서륜
cytochrome P450%HPLC%chlorzoxazone%tolbutamide%midazolam
目的:建立同时测定大鼠血浆中细胞色素 P450(CYP450)酶探针药物氯唑沙宗、甲苯磺丁脲和咪达唑仑浓度的高效液相色谱法。方法色谱柱采用 Diamonsil C18(250 mm ×4.6 mm,5μm),流动相为甲醇与磷酸二氢铵缓冲液(61∶39,V /V),流速1 mL·min -1,检测波长230 nm,带宽4 nm,柱温35℃,以地西泮为内标,同时检测氯唑沙宗、甲苯磺丁脲和咪达唑仑的大鼠血浆药物浓度。结果氯唑沙宗、甲苯磺丁脲和咪达唑仑均在0.1~50 mg·L -1(r =0.9995)的范围内线性关系良好;低、中、高3个浓度下,3种探针药物精密度试验中相对标准偏差为4.78%~9.78%,回收率为92.71%~109.79%。结论该方法操作简便,灵敏度高,重现性好,符合生物样品分析要求,适用于同时测定3种 CYP450酶亚型探针药物氯唑沙宗、甲苯磺丁脲和咪达唑仑的大鼠血浆药物浓度,可为 CYP450酶活性测定提供分析方法学参考。
目的:建立同時測定大鼠血漿中細胞色素 P450(CYP450)酶探針藥物氯唑沙宗、甲苯磺丁脲和咪達唑崙濃度的高效液相色譜法。方法色譜柱採用 Diamonsil C18(250 mm ×4.6 mm,5μm),流動相為甲醇與燐痠二氫銨緩遲液(61∶39,V /V),流速1 mL·min -1,檢測波長230 nm,帶寬4 nm,柱溫35℃,以地西泮為內標,同時檢測氯唑沙宗、甲苯磺丁脲和咪達唑崙的大鼠血漿藥物濃度。結果氯唑沙宗、甲苯磺丁脲和咪達唑崙均在0.1~50 mg·L -1(r =0.9995)的範圍內線性關繫良好;低、中、高3箇濃度下,3種探針藥物精密度試驗中相對標準偏差為4.78%~9.78%,迴收率為92.71%~109.79%。結論該方法操作簡便,靈敏度高,重現性好,符閤生物樣品分析要求,適用于同時測定3種 CYP450酶亞型探針藥物氯唑沙宗、甲苯磺丁脲和咪達唑崙的大鼠血漿藥物濃度,可為 CYP450酶活性測定提供分析方法學參攷。
목적:건립동시측정대서혈장중세포색소 P450(CYP450)매탐침약물록서사종、갑분광정뇨화미체서륜농도적고효액상색보법。방법색보주채용 Diamonsil C18(250 mm ×4.6 mm,5μm),류동상위갑순여린산이경안완충액(61∶39,V /V),류속1 mL·min -1,검측파장230 nm,대관4 nm,주온35℃,이지서반위내표,동시검측록서사종、갑분광정뇨화미체서륜적대서혈장약물농도。결과록서사종、갑분광정뇨화미체서륜균재0.1~50 mg·L -1(r =0.9995)적범위내선성관계량호;저、중、고3개농도하,3충탐침약물정밀도시험중상대표준편차위4.78%~9.78%,회수솔위92.71%~109.79%。결론해방법조작간편,령민도고,중현성호,부합생물양품분석요구,괄용우동시측정3충 CYP450매아형탐침약물록서사종、갑분광정뇨화미체서륜적대서혈장약물농도,가위 CYP450매활성측정제공분석방법학삼고。
Objective To establish an efficient,rapid,selective HPLC method for determining three CYP450s probe drugs,chlorzoxa-zone,tolbutamide and midazolam,in single run in rat plasma.Methods The three specific probe substrates of chlorzoxazone,tolbuta-mide,and midazolam,together with the internal standard diazepam,could be extracted using liquid-liquid extraction in rat plasma,fol-lowed by high-performance liquid chromatography (HPLC)using a C18 column (250 mm ×4.6 mm,5 μm).The mobile phase was con-stituted of a methanol and 0.05 mol·L -1 phosphate buffer (61∶39,V /V).Results All analytes were separated simultaneously in a single run .The detection limits ranged from 0.1 ~50 mg·L -1 for chlorzoxazone,tolbutamide and midazolam.The precisions for three probe substrates were 4.78% ~9.78%,the accuracy of three probe substrates ranged from 92.71% ~109.79%.The limit of quantifica-tion (LOQ)was 0.1 mg·L -1 for chlorzoxazone,tolbutamide and midazolam.Conclusions The present method provides a robust,fast analytical tool for the three-probe drug cocktail.Finally,the method was suitable for determining the plasma concentration of these com-pounds and evaluating the CYP2E1,CYP2C9 and CYP3A4 activities in the drug-drug interaction studies.