Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
J Pharm Biomed Anal. 2012 Dec;71:99-103. doi: 10.1016/j.jpba.2012.08.010. Epub 2012 Aug 17.
Oxaliplatin is a platinum agent that is used for treatment of colorectal cancer. A sensitive and selective hydrophilic interaction liquid chromatography-tandem mass spectrometric method for the quantification of oxaliplatin was developed. Human plasma ultrafiltrates were precipitated by acetonitrile containing carboplatin as an internal standard and further diluted with acetonitrile. Chromatographic separation of oxaliplatin and the internal standard was achieved with a column modified with phosphorylcholine and an isocratic mobile phase (acetonitrile/water/acetic acid=90:10:0.1, v/v/v) at the flow rate of 0.2mL/min. The lower limit of quantification for oxaliplatin was 25ng/mL. The linearity range of the method was from 25 to 5000ng/mL. The intra-day precision and inter-day precision (RSD) ranged from 0.8 to 6.1%, and the accuracy (RE) was within ±4.5%. The extraction recoveries from human plasma ultrafiltrates were 83.6-91.6%, and ion suppression caused by matrix components was 86.7-88.5% at three different levels, respectively. This method was applied to a clinical pharmacokinetic study of oxaliplatin in a cancer patient. The maximum concentration of colorectal cancer patient administered oxaliplatin was 1650ng/mL.
奥沙利铂是一种铂类药物，用于治疗结直肠癌。本研究建立了一种灵敏、选择性的亲水作用色谱-串联质谱法，用于奥沙利铂的定量分析。以卡铂为内标，用含乙腈的溶液沉淀人血浆超滤液，然后用乙腈进一步稀释。采用带有膦酰胆碱修饰的色谱柱，以乙腈/水/乙酸（90:10:0.1，v/v/v）为流动相，等度洗脱，流速为 0.2mL/min，实现了奥沙利铂和内标的色谱分离。奥沙利铂的定量下限为 25ng/mL。方法的线性范围为 255000ng/mL。日内和日间精密度（RSD）范围为 0.8%6.1%，准确度（RE）在±4.5%范围内。人血浆超滤液的提取回收率为 83.6%91.6%，基质成分引起的离子抑制率为 86.7%88.5%，分别在三个不同浓度水平。本方法应用于癌症患者奥沙利铂的临床药代动力学研究。接受奥沙利铂治疗的结直肠癌患者的最大血药浓度为 1650ng/mL。
