Lepper Erin R, Hicks J Kevin, Verweij Jaap, Zhai Suoping, Figg William D, Sparreboom Alex
Clinical Pharmacology Research Core, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Building 10, Room 5A01, Bethesda, MD 20892, USA.
J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Jul 5;806(2):305-10. doi: 10.1016/j.jchromb.2004.04.003.
A liquid chromatographic assay with mass-spectrometric detection was developed for the quantitative determination of the cytochrome p450 3A phenotyping probe midazolam in human plasma. Sample pretreatment involved a one-step extraction of 600 microl aliquots with ethyl acetate. Midazolam and the internal standard, lorazepam, were separated on a column (150 mm x 4.6mm, i.d.) packed with 5 microm Zorbax Eclipse XDB-C8 material, using a mobile phase composed of methanol and 10mM aqueous ammonium acetate (60:40, v/v). Column effluents were analyzed using mass-spectrometry with an atmospheric pressure chemical ionization source. Calibration curves were linear in the concentration range of 1.00-200 ng/ml. The accuracy and precision ranged from 92.8 to 112% and 0.056 to 13.4%, respectively, for four different concentrations of quality control samples analyzed in triplicate on eight separate occasions. The developed method was subsequently applied to study the pharmacokinetics of midazolam in a group of 35 human subjects at a single dose of 25 microg/kg.
建立了一种采用质谱检测的液相色谱法，用于定量测定人血浆中细胞色素P450 3A表型探针咪达唑仑。样品预处理包括用乙酸乙酯对600微升等分试样进行一步萃取。咪达唑仑和内标物劳拉西泮在填充有5微米Zorbax Eclipse XDB - C8材料的色谱柱（150毫米×4.6毫米，内径）上分离，流动相由甲醇和10毫摩尔/升乙酸铵水溶液（60:40，v/v）组成。使用大气压化学电离源的质谱对柱流出物进行分析。校准曲线在1.00 - 200纳克/毫升的浓度范围内呈线性。在八个不同场合对四种不同浓度的质量控制样品进行三次重复分析，准确度范围为92.8%至112%，精密度范围为0.056%至13.4%。随后将所建立的方法应用于研究35名人类受试者单次给予25微克/千克剂量的咪达唑仑的药代动力学。
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