Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Jul 15;879(22):2162-70. doi: 10.1016/j.jchromb.2011.05.057. Epub 2011 Jun 13.
The main purpose of this study was to develop and validate a rapid, specific, sensitive, and reliable LC-MS/MS-based bioanalytical method for the determination of carboplatin in human plasma. The optimal chromatographic behavior of carboplatin was achieved on a Biobasic SCX column (50 mm × 2.1 mm, 5 μm) using ion exchange chromatography. The total LC analysis time per injection was 2.6 min with a flow rate of 1.5 mL/min with a gradient elution. Optimization with regard to improving recovery and minimizing matrix effects using HybridSPE-precipitation (HybridSPE-PPT) has been evaluated under various extraction conditions. As a result, sample preparation via HybridSPE-PPT with 1% formic acid in acetonitrile in a 96-well format was applied for method validation and sample analysis and showed acceptable recovery of greater than 25% and negligible matrix effects. The method validation was conducted over the curve range of 2.00-2000 ng/mL using 0.0500 mL of plasma sample. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels showed ≤4.8% relative standard deviation (RSD) and -13.2 to -3.6% relative errors (RE). The method was successfully applied to determine carboplatin in human plasma samples.
本研究的主要目的是开发和验证一种用于测定人血浆中卡铂的快速、特异、灵敏和可靠的 LC-MS/MS 生物分析方法。采用离子交换色谱法，在 Biobasic SCX 柱（50mm×2.1mm，5μm）上实现了卡铂的最佳色谱行为。每次进样的总 LC 分析时间为 2.6 分钟，流速为 1.5mL/min，采用梯度洗脱。采用 HybridSPE-沉淀（HybridSPE-PPT）优化回收率和最小化基质效应，在各种提取条件下进行了评估。结果表明，采用 96 孔格式的 1%甲酸乙腈中的 HybridSPE-PPT 进行样品制备，适用于方法验证和样品分析，回收率大于 25%，基质效应可忽略不计。该方法在 2.00-2000ng/mL 的曲线范围内进行验证，使用 0.0500mL 血浆样品。低、中、高浓度质控样品的日内和日间精密度和准确度均显示≤4.8%相对标准偏差（RSD）和-13.2 至-3.6%相对误差（RE）。该方法成功应用于测定人血浆样品中的卡铂。
