高效液相色谱-质谱法测定比格犬血浆中的艾普拉唑及其药代动力学  

Determination of ilaprazole in beagle plasma and its pharmacokinetics by high performance liquid chromatography-mass spectrometry

作　　者：周丽君[1,2] 李敬来[2] 王晓英[2] 乔建忠[2] 张振清[2] 

机构地区：[1]中国人民解放军总医院,北京100853 [2]军事医学科学院毒物药物研究所,北京100850

出　　处：《色谱》2012年第5期452-456,共5页Chinese Journal of Chromatography

基　　金：国家重大新药创制综合性大平台(2009ZX09301-002);国家重大新药创制单元平台(2009ZX09304-004)

摘　　要：运用高效液相色谱-电喷雾质谱(HPLC-ESI-MS)技术,建立了快速、简单、灵敏的比格犬静脉滴注艾普拉唑钠盐后血药浓度的检测方法。血浆样品采用蛋白沉淀法,以丁螺环酮作为内标,色谱柱为Teknokroma Kromasil C18(100 mm×2.1 mm,5μm),流动相为水-甲醇-乙腈(69∶8∶23,v/v/v)(含0.1%的甲酸),流速0.2 mL/min,采用电喷雾(ESI)离子源以正离子方式检测。绘制血药浓度-时间曲线,并采用DAS 2.0计算药代动力学参数。方法学实验结果表明内源性杂质不干扰艾普拉唑和内标的测定,线性范围为5～10 000μg/L(r=0.994),最低定量限为5μg/L,精密度和准确度均符合生物样品测定的要求。低、中、高3个浓度的绝对回收率在106%左右,基质效应小于142.0%,表明该方法适合比格犬血浆中艾普拉唑浓度的测定及药代动力学研究。比格犬静脉滴注艾普拉唑钠盐3个剂量(0.2 mg/kg、0.8 mg/kg和3.2 mg/kg)后的药-时曲线下面积(AUC(0-∞))分别为(2.4×104±3×103)、(8.8×104±1.6×104)和(5.4×105±8×104)μg/L.min,呈线性药物代谢动力学过程。A sensitive,simple and specific high performance liquid chromatography-electrospray ionization mass spectrometry method was developed for the determination of ilaprazole in the plasma of beagles administered via i.v.bolus doses of ilaprazole.The procedure employed buspirone as the internal standard and a simple protein precipitation step.The separation was achieved using a C18 column（100 mm×2.1 mm,5 μm） with a mobile phase consisting of water-methanol-acetonitrile（69∶8∶23,v/v/v） containing 0.1%（v/v） formic acid at a flow rate of 0.2 mL/min.The detection was accomplished by a mass spectrometer using selected ion monitoring（SIM） in positive mode.The linearity was from 5 μg/L to 10 000 μg/L with a sensitivity of 5 μg/L as the lower limit of quantification.The inter-and intra-day precisions were within 9.00%.The mean recoveries at three spiked levels were about 106% and the matrix effects were less than 142.0%.The method described above was successfully applied to analyze the beagle plasma samples of ilaprazole in a pharmacokinetic study.The area under the plasma concentration-time curve（AUC（0-∞））of ilaprazole after i.v.doses of 0.2,0.8 and 3.2 mg/kg were（2.4×104±3×103）、（8.8×104±1.6×104） and（5.4×105±8×104） μg/L·min,respectively.On the basis of AUC,the pharmacokinetic property of ilaprazole was proposed to be linear dynamics.

关 键 词：高效液相色谱-电喷雾质谱 艾普拉唑 比格犬血浆 药代动力学 

分 类 号：O658[理学—分析化学]