LC-MS/MS法测定小鼠血浆及组织中伊曲康唑浓度___

建立LC-MS/MS法测定小鼠血浆及组织中伊曲康唑的浓度。方法：以尼莫地平为内标，采用乙腈-水-甲酸（80∶20∶02）为流动相，以Waters XTerra MS-C18色谱柱（21 mm×150 mm，35 μm）为分析柱，流速为02 mL ·min-1，采用电喷雾电离（ESI），以多反应离子监测（MRM）方式进行正离子检测。用于定量分析的离子反应分别为m/z 7053→3921（伊曲康唑）和m/z 4193→3433（内标，尼莫地平）。结果：测定血浆及组织中伊曲康唑的线性范围为100~16000 μg·L-1，定量下限为100 μg ·L-1。日内、日间精密度（RSD）小于97%，方法回收率为990%~1098%。结论：本方法灵敏度高、专属性强、操作简便，适用于伊曲康唑脂质体在小鼠体内组织分布研究。 关键词：伊曲康唑；LC-MS/MS法；脂质体；组织分布

To establish an LC-MS/MS method for the determination of itraconazole in plasma and tissue of mice.Methods:A Waters XTerraMS-C18 column(21 mm×150 mm,35 μm)was adopted with the mobile phase consisted of acetonitrile-water-formic acid(80∶20∶02,v/v/v)at a flow rate of 020 mL·min-1.Nimodipine was used as the internal standard.Waters Micromass Quattro API tandem mass spectrometer equipped with electrospray ionization source(ESI)was used as detector operated in the positive ion mode.Multiple reaction monitoring(MRM)with the precursor to product ion combinations of m/z 7053→3921 and m/z 4193→3433 were performed to quantify itraconazole and the internal standard(nimodipine),respectively.Results:The linear calibration curves were obtained in the concentration range of 100-16000 μg · L-1.The lowest limit of quantification was 100 μg·L-1 .The inter-and intra-day precision(RSD)was less than 97%.The method recoveries were within 990%~1098%.Conclusion: The method was proved to be sensitive,rapid,convenient and suitable for tissue distribution of itraconazole liposomes in mice.

1Karel DB,Jef VGPharmacology of itraconazoleDrugs,2001,61(1):27 2CAI Yong-ning(蔡永宁),LIANG De-rong(梁德容),ZHU Huan-ling(朱焕玲),et al.Efficacy and safety of itraconazole injection in treatment of deep fungal infecfions(伊曲康唑注射液治疗深部真菌感染).Chin J New Drugs (中国新药杂志),2004,13(2):161 3SUN Zhong-shi(孙忠实),ZHU Zhu(朱珠).The observation of itraconazole injection（伊曲康唑注射液评述）.Chin Pharm J(中国药学杂志),2003,38(8):630 4DONG Di(董迪),LIU Hong-mei(刘红梅),SONG Xiao-dan(宋笑丹), et al.RP-HPLC determination of itraconazole liposomes and its entrapment efficiency(反向高效液相色谱法测定伊曲康唑脂质体药物含量及包封率).Chin J Pharm Anal (药物分析杂志),2007,27(9):1453 5Vijaya DB,Kishore KH,Vidya PP,et al.Development and validation of a highly sensitive and robust LC MS/MS with electrospray ionization method for simultaneous quantitation of itraconazole and hydroxyitraconazole in human plasma:Application to a bioequivalence study.J Chromatogr B,2008,868:70 6Tomoya O,Kazuki N,Susumu N,et al.Effect of itraconazole on the pharmacokinetics of imidafenacin in healthy subjects.J Clin Pharmacol,2008,48(3):330 7Tell LA,Craigmill AL,Clemons KV,et al.Studies on itraconazole delivery and pharmacokinetics in mallard ducks.J Vet Pharmacol Ther,2005,28:267 8Jee HS,Ka YC,Yu CK,et al.Dose-dependent pharmacokinetics of itraconazole after iIntravenous or oral administration to rats:intestinal first-pass effect.Antimicrob Agents Chemother,2004,48(5):1756 9Jason TM,Krik AO,Praposri S,et al.Targeted high lung concentrations of itraconazole using nebulized dispersions in a murine model.Pharm Res,2006,23(5):901 10CHEN Li-juan(陈丽娟).Determination of itraconazole in human plasma by HPLC(HPLC测定人血浆中伊曲康唑的浓度).West China J Pharm Sci(华西药学杂志),2006,21(3):293 11CHEN Jun(陈均)，JIANG Wen-ming(江文明),ZHANG Min(张敏),et al．HPLC determination of itraconazole and its metabolite hydroxyltraconazole in human plasma (HPLC测定人血浆中伊曲康唑及其代谢产物羟基伊曲康唑的浓度).Chin J Pharm Anal (药物分析杂志),2005,25(7):756 12ZHAO Yan(赵雁),YUE Peng(岳鹏),TAO Tao(陶涛),et al.Pharmacokinetics of itraconazole hydrochloride dispersible tablets in Beagle dogs(盐酸伊曲康唑分散片在Beagle犬体内的药动学研究).Chin Pharm J(中国药学杂志),2005,40(18):1412