中国临床药理学杂志
中國臨床藥理學雜誌
중국림상약이학잡지
The Chinese Journal of Clinical Pharmacology
2015年
18期
1873-1876
,共4页
乔丽曼%王豪%楼旦%黄成坷
喬麗曼%王豪%樓旦%黃成坷
교려만%왕호%루단%황성가
超高液相色谱-质谱法%格列美脲%羟基格列美脲%氟西汀%去甲氟西汀
超高液相色譜-質譜法%格列美脲%羥基格列美脲%氟西汀%去甲氟西汀
초고액상색보-질보법%격렬미뇨%간기격렬미뇨%불서정%거갑불서정
UPLC-MS/MS%glimepiride%hydroxy glimepiride%fluoxetine%norfluoxetine
目的：建立一种同时检测人血浆中格列美脲、氟西汀及其代谢物羟基格列美脲、去甲氟西汀浓度的超高液相色谱-质谱的方法。方法以咪达唑仑为内标，血浆样品用乙腈沉淀后检测。用Acquity UPLC BEH C 18柱为分离柱，流动相：乙腈-0.1％甲酸，梯度洗脱，流速：0.45 mL· min-1，柱温：40℃；用Acquity Xevo TQD三重四级杆质谱仪（电喷雾离子源）质谱检测，用多反应监测法测定样品中的药物浓度。考察该方法的专属性、标准曲线和定量下限、精密度和回收率、基质效应及稳定性。结果格列美脲、羟基格列美脲、氟西汀和羟基氟西汀的标准曲线分别为y=1.49×10-2 x+4.23×10-2（ r=0.9997）， y=0.97×10-2 x-0.26×10-2（ r=0.9995）， y=1.72×10-2 x+9.48×10-2（ r=0.9993）， y=8.66×10-2x-1.05×10-2（r=0.9994），分别在5~1000，2.5~500，1~200，0.5~100 ng· mL-1线性关系良好。药物及其代谢物的回收率均大于90％，日内、日间精密度均小于15％。结论该方法简便、快速，可用于人血浆格列美脲、氟西汀及其代谢产物的检测、药代动力学研究和药物相互作用研究。
目的：建立一種同時檢測人血漿中格列美脲、氟西汀及其代謝物羥基格列美脲、去甲氟西汀濃度的超高液相色譜-質譜的方法。方法以咪達唑崙為內標，血漿樣品用乙腈沉澱後檢測。用Acquity UPLC BEH C 18柱為分離柱，流動相：乙腈-0.1％甲痠，梯度洗脫，流速：0.45 mL· min-1，柱溫：40℃；用Acquity Xevo TQD三重四級桿質譜儀（電噴霧離子源）質譜檢測，用多反應鑑測法測定樣品中的藥物濃度。攷察該方法的專屬性、標準麯線和定量下限、精密度和迴收率、基質效應及穩定性。結果格列美脲、羥基格列美脲、氟西汀和羥基氟西汀的標準麯線分彆為y=1.49×10-2 x+4.23×10-2（ r=0.9997）， y=0.97×10-2 x-0.26×10-2（ r=0.9995）， y=1.72×10-2 x+9.48×10-2（ r=0.9993）， y=8.66×10-2x-1.05×10-2（r=0.9994），分彆在5~1000，2.5~500，1~200，0.5~100 ng· mL-1線性關繫良好。藥物及其代謝物的迴收率均大于90％，日內、日間精密度均小于15％。結論該方法簡便、快速，可用于人血漿格列美脲、氟西汀及其代謝產物的檢測、藥代動力學研究和藥物相互作用研究。
목적：건립일충동시검측인혈장중격렬미뇨、불서정급기대사물간기격렬미뇨、거갑불서정농도적초고액상색보-질보적방법。방법이미체서륜위내표，혈장양품용을정침정후검측。용Acquity UPLC BEH C 18주위분리주，류동상：을정-0.1％갑산，제도세탈，류속：0.45 mL· min-1，주온：40℃；용Acquity Xevo TQD삼중사급간질보의（전분무리자원）질보검측，용다반응감측법측정양품중적약물농도。고찰해방법적전속성、표준곡선화정량하한、정밀도화회수솔、기질효응급은정성。결과격렬미뇨、간기격렬미뇨、불서정화간기불서정적표준곡선분별위y=1.49×10-2 x+4.23×10-2（ r=0.9997）， y=0.97×10-2 x-0.26×10-2（ r=0.9995）， y=1.72×10-2 x+9.48×10-2（ r=0.9993）， y=8.66×10-2x-1.05×10-2（r=0.9994），분별재5~1000，2.5~500，1~200，0.5~100 ng· mL-1선성관계량호。약물급기대사물적회수솔균대우90％，일내、일간정밀도균소우15％。결론해방법간편、쾌속，가용우인혈장격렬미뇨、불서정급기대사산물적검측、약대동역학연구화약물상호작용연구。
Objective To develop an ultra -high performance liquid chromatography-mass spectrometry method to determination the plasma concentration of glimepiride(GLP), fluoxetine(FLU) and their metabo-lites-hydroxy glimepiride ( M1 ) and norfluoxetine ( NFLU) in human. Methods Midazolam was used as internal standard ( IS ) , plasma was precipited by acetonitrile .Chromatographic separation was carried out on an Acquity UPLC BEH C 18 column.A mixture of acetonitrile-0.1%for-mic acid was used as the mobile phase with the flow rate at 0.45 mL· min-1 , gradient elution.The column temperature was set at 40 ℃.The mass spectrometric analysis was performed using an Acquity Xevo TQD triple quadrupole mass spectrometer coupled with an electro -spray ionization(ESI) source in the positive ion mode.The multiple re-action monitoring was used to determination the drug concentration in the samples.Results The standard curve of GLP , M1, FLU, NFLU were y=1.49 ×10 -2 x +4.23 ×10 -2 ( r =0.999 7 ) , y =0.97 ×10 -2 x -0.26 ×10 -2 ( r =0.999 5 ) , y =1.72 × 10 -2 x +9.48 × 10 -2 ( r=0.999 3 ) , y =8.66 ×10 -2 x -1.05 ×10 -2 ( r =0.999 4 ) ,respectively.The linearities were within the concentration range of 5 -1000 , 2.5 -500 , 1 -200 , 0.5 -100 ng· mL-1 for GLP, M1, FLU and NFLU in human plasma.The recoveries of four analytes were greater than 90%, the intra and inter-day precision were less than 15%.Conclusion The method is simple , rapid and suitable for the quantitative determination of plasma glimepiride , fluoxetine and their metabolites , pharmacokinetic and drug interaction studies.
