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Development and Validation of an Inductively Coupled Plasma Mass Spectrometry (ICP-MS) Method for Quantitative Analysis of Platinum in Plasma Urine and Tissues

机译:等离子体尿液和组织中铂的定量分析的电感耦合等离子体质谱法(ICP-MS)的开发和验证

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摘要

Cisplatin, a platinum chemotherapeutic, is one of the most commonly used chemotherapeutic agents for many solid tumors. In this work, we developed and validated an inductively coupled plasma mass spectrometry (ICP-MS) method for quantitative determination of platinum levels in rat urine, plasma, and tissue matrices including liver, brain, lungs, kidney, muscle, heart, spleen, bladder, and lymph nodes. The tissues were processed using a microwave accelerated reaction system (MARS) system prior to analysis on an Agilent 7500 ICP-MS. According to the Food and Drug Administration guidance for industry, bioanalytical validation parameters of the method, such as selectivity, accuracy, precision, recovery, and stability were evaluated in rat biological samples. Our data suggested that the method was selective for platinum without interferences caused by other presenting elements, and the lower limit of quantification was 0.5 ppb. The accuracy and precision of the method were within 15% variation and the recoveries of platinum for all tissue matrices examined were determined to be 85–115% of the theoretical values. The stability of the platinum-containing solutions, including calibration standards, stock solutions, and processed samples in rat biological matrices was investigated. Results indicated that the samples were stable after three cycles of freeze–thaw and for up to three months.
机译:顺铂是一种铂类化学疗法,是许多实体瘤中最常用的化学疗法之一。在这项工作中,我们开发并验证了电感耦合等离子体质谱(ICP-MS)方法,用于定量测定大鼠尿液,血浆和组织基质(包括肝,脑,肺,肾,肌肉,心脏,脾脏,膀胱和淋巴结。在使用Agilent 7500 ICP-MS进行分析之前,使用微波加速反应系统(MARS)系统对组织进行处理。根据食品和药物管理局的工业指南,在大鼠生物样品中评估了该方法的生物分析验证参数,例如选择性,准确性,精密度,回收率和稳定性。我们的数据表明,该方法对铂具有选择性,没有其他呈递元素引起的干扰,定量下限为0.5 ppb。该方法的准确性和精密度相差15%以内,测定的所有组织基质的铂回收率均为理论值的85–115%。研究了含铂溶液在大鼠生物基质中的稳定性,包括校准标准液,储备溶液和处理过的样品。结果表明,样品经过三个冷冻-融化循环后稳定了三个月。

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