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采用亲水相互作用液相色谱-串联质谱法对人血浆超滤物中的全顺式卡铂进行定量分析及其在药代动力学研究中的应用。

Quantification of intact carboplatin in human plasma ultrafitrates using hydrophilic interaction liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

机构信息

Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Feb 15;917-918:18-23. doi: 10.1016/j.jchromb.2012.11.024. Epub 2012 Dec 3.

DOI:10.1016/j.jchromb.2012.11.024
PMID:23348368
Abstract

Carboplatin is a platinum agent that is used for treatment of non-small-cell lung cancer and ovarian cancer. A sensitive and selective analytical method for the quantification of carboplatin in human plasma ultrafiltrates using liquid chromatography-tandem mass spectrometry was developed. Human plasma ultrafiltrates were precipitated by acetonitrile containing carboplatin-d4 as an internal standard and were further diluted with acetonitrile. Chromatographic separation was performed on a Accucore HILIC (50mm×2.1mm i.d., 2.6μm) column using mobile phase (acetonitrile-water-acetic acid=90:10:0.1, v/v/v) at the flow rate of 0.2mL/min. Detection was performed on electrospray ionization triple quadrupole tandem mass spectrometer using low-energy collision induced dissociation (CID-MS/MS) analysis operating in the selected reaction monitoring (SRM) scan mode. The lower limit of quantification for carboplatin was 0.025μg/mL. This method covered a linearity range of 0.025-50μg/mL. The intra-day precision and inter-day precision (R.S.D.) ranged from 1.5 to 4.3%, and the accuracy (R.E.) was within ±2.9%. The present method was applied to a clinical pharmacokinetic study of carboplatin in a cancer patient.

摘要

卡铂是一种铂类药物,用于治疗非小细胞肺癌和卵巢癌。建立了一种灵敏、专属性的液相色谱-串联质谱法,用于人血浆超滤液中卡铂的定量分析。用人血浆超滤液沉淀含卡铂-d4(内标)的乙腈,再用乙腈稀释。采用 Accucore HILIC(50mm×2.1mm i.d.,2.6μm)柱,以乙腈-水-冰醋酸(90:10:0.1,v/v/v)为流动相,流速为 0.2mL/min 进行色谱分离。在电喷雾电离三重四极杆串联质谱仪上,采用低能量碰撞诱导解离(CID-MS/MS)分析,在选择反应监测(SRM)扫描模式下进行检测。卡铂的定量下限为 0.025μg/mL。该方法的线性范围为 0.025-50μg/mL。日内精密度和日间精密度(RSD)为 1.5%-4.3%,准确度(RE)为±2.9%。该方法应用于癌症患者卡铂的临床药代动力学研究。

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