人们越来越关注使用不同的液相色谱技术与质谱联用来定量人血浆中的铂类抗癌药物，从而为癌症化疗提供信息。我们开发、验证和研究了一种使用超高效液相色谱联用电感耦合等离子体质谱 (UHPLC-ICP-MS) 定量人血浆中完整奥沙利铂的方法。从患者处采集血浆样本后立即进行处理，通过甲醇脱蛋白保存奥沙利铂形态，并将稀释的上清液（血浆：甲醇 1:2 v/v）储存在 -80 °C 下。使用 C18 柱和线性梯度流动相（流动相 A：水-甲醇 (97:3 v/v)、0.075 mM 十二烷基硫酸钠、9.79 nM 铊，调整至pH 2.5，三氟甲磺酸；流动相 B：100% 甲醇 (v/v))，采用 ICP-MS 检测，分别在 m/z 195 和 205 处监测铂和铊。甲醇脱蛋白稀释血浆 (1:2 v/v) 中的定量限为 50 nM。在甲醇脱蛋白稀释血浆 (1:2 v/v) 中制备的 50 至 500 nM 范围内的校准标准品以及在含有内标的空白基质中稀释较高浓度样品（最终稀释度 1:29 v/v）建立了线性关系）。日内和日间准确度范围为标称浓度的 96.8% 至 103%，精密度范围为 0.62% 至 2.49% 变异系数。回收已完成，基质效应证实了基质匹配标准品的要求。完整的奥沙利铂在甲醇脱蛋白稀释血浆（1:2 v/v）中储存至少 473 天期间以及分析期间保持稳定。该方法用于测定接受癌症化疗的患者中完整奥沙利铂的血浆浓度，以及奥沙利铂的体外降解研究。这种基于 UHPLC-ICP-MS 的改进方法将能够对人血浆中完整的奥沙利铂进行更特异、高效和可靠的定量。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

Interest is increasing in the use of different liquid chromatography techniques coupled online to mass spectrometry for the quantification of platinum anticancer drugs in human plasma to inform cancer chemotherapy. We developed, validated and studied the application of a method for quantification of intact oxaliplatin in human plasma using ultra high performance liquid chromatography hyphenated to inductively coupled plasma mass spectrometry (UHPLC-ICP-MS). Plasma samples were processed instantly after collection from patients to preserve oxaliplatin speciation by methanol-deproteinization, and storage of diluted supernatants (plasma:methanol 1:2 v/v) at -80 °C. UHPLC separation of intact oxaliplatin and internal standard (carboplatin) was achieved using a C18 column and linear gradient mobile phase (Mobile phase A: water-methanol (97:3 v/v), 0.075 mM sodium dodecyl sulfate, 9.79 nM thallium adjusted to pH 2.5 with trifluoromethanesulfonic acid; Mobile phase B: 100 % methanol (v/v)) with ICP-MS detection to monitor platinum and thallium at m/z 195 and 205, respectively. The limit of quantification was 50 nM in methanol-deproteinized diluted plasma (1:2 v/v). Linearity was established for calibration standards ranging from 50 to 500 nM made in methanol-deproteinized diluted plasma (1:2 v/v), and for dilution of higher concentration samples in blank matrix containing internal standard (final dilution 1:29 v/v). Intra-day and inter-day accuracy ranged from 96.8 to 103 % of nominal concentration and precision from 0.62 to 2.49 % coefficient of variation. Recovery was complete and a matrix effect confirmed the requirement for matrix-matched standards. Intact oxaliplatin was stable during storage for at least 473 days, and during analysis, in methanol-deproteinized diluted plasma (1:2 v/v). The method was applied to determining the plasma concentrations of intact oxaliplatin in patients undergoing cancer chemotherapy, and studies of oxaliplatin degradation in vitro. This improved method based on UHPLC-ICP-MS will allow more specific, efficient and reliable quantification of intact oxaliplatin in human plasma.Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.