【作者】 于华玲；

【导师】 陈笑艳； 钟大放；

【作者基本信息】 沈阳药科大学 ， 药物分析学， 2006， 硕士

【摘要】 本文有两部分组成。一、液相色谱-串联质谱法测定血浆中的氟桂利嗪目的：建立专属、灵敏的液相色谱-串联质谱法测定人血浆中氟桂利嗪的浓度。方法：0.25 mL血浆样品经液-液萃取后，以乙腈-水-甲酸（80∶20∶0.5，v／v／v）为流动相，Zorbax SB C₁₈柱分离，通过大气压化学电离源四极杆串联质谱，以选择反应监测方式进行检测。用于定量分析的离子反应分别为m／z 405→m／z 203（氟桂利嗪）和m／z 256→m／z 167（内标，苯海拉明）。结果：测定血浆中氟桂利嗪方法的线性范围为0.2～200 ng／mL，定量下限为0.2ng／mL。日内、日间精密度（RSD）均小于6.5％，准确度（RE）在±0.9％以内。结论：该方法选择性强，灵敏度高，适用于氟桂利嗪临床药动学研究。二、血浆中HV-08的定量分析方法研究目的：建立快速、灵敏的液相色谱-串联质谱法测定血浆中的HV-08，研究HV-08在Wistar大鼠和Beagle犬体内的药物动力学性质。方法：血浆样品经沉淀蛋白提取，以苯海拉明为内标，流动相为甲醇-水-甲酸（60∶40∶0.2，v／v／v），采用Diamonsil C₁₈柱进行色谱分离，通过大气压化学电离源四极杆串联质谱，以选择反应监测方式进行检测。用于定量分析的离子反应分别为m／z 563→m／z 58 （HV-08）和m／z 256→m／z 167（内标，苯海拉明）。结果：该法用于测定HV-08的线性范围为0.75～1000 ng／mL，定量下限为0.75 ng／mL。应用本法对Wistar大鼠和Beagle犬分别静脉注射和三个剂量组灌胃给予HV-08后的药物动力学进行研究。结论：该方法选择性强，灵敏度高，适用于临床前药动学研究。更多还原

【Abstract】 Two rapid, sensitive and specific LC/MS/MS methods for quantitative analyses of flunarizine and HV-08 in plasma were developed and validated.1. Determination of flunarizine in plasma by LC/MS/MSObjective To develop a sensitive and specific LC/MS/MS method for determination of flunarizine in human plasma. Methods Flunarizine and internal standard diphenhydramine were extracted from 0.25 mL plasma using liquid-liquid extraction, then separated on a Zorbax SB C₁₈ column. The mobile phase consisted of acetonitrile-water-formic acid （80: 20: 0.5, v/v/v）. A Finnigan TSQ tandem mass spectrometer equipped with atmospheric pressure chemical ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring mode using the precursor to product ion of m/z 405 to m/z 203 and m/z 256 to m/z 167 was performed to quantify flunarizine and the internal standard respectively. Results The linear calibration curves were obtained in the concentration range of 0.2-200 ng/mL. The lower limit of quantification was 0.2 ng/mL. The inter- and intra-day precision （RSD） was below 6.5 %, and the accuracy （RE） was within±0.9 % calculated from QC samples. Conclusion The method was proved to be specific, sensitive, and suitable for clinical investigation of flunarizine pharmacokinetics.2. Quantitative analyses of HV-08 in plasma by LC/MS/MSObjective To develop a rapid, sensitive and highly selective liquid chromatography-tandem mass spectrometry method for determination of HV-08 in plasma. Methods The analytes were extracted from plasma samples by protein precipitation, separated on a Diamonsil C₁₈ column and detected by tandem mass spectrometry with an atmospheric pressure chemical ionization source. The mobile phase consisted of methanol-water-formic acid （60:40:0.2, v/v/v）. Diphenhydramine was used as the internal standard. Selected reaction monitoring using the precursor→product ion combinations of m/z 563→m/z 58 and m/z 256→m/z 167 was used to quantify HV-08 and internal standard, respectively. Results The method has a lower limit of quantification （LLOQ） of 0.75 ng/mL for HV-08. The linear calibration curves were obtained in the concentration range of 0.75-1000 ng/mL. The method was applied to study the pharmacokinetics of HV-08 in rats and dogs after oral and i.v. injection administration of HV-08. Conclusion The method was proved to be specific, sensitive, and suitable for investigation of HV-08 pharmacokinetics in rats and dogs.更多还原