利用超滤和沉淀方法测定人体血浆中的非结合铂浓度。

IF 1.3 4区 医学 Q4 PHARMACOLOGY & PHARMACY
Xia Wen , Cathleen Doherty , Lauren E. Thompson , Christine Kim , Brian S. Buckley , Edgar A. Jaimes , Melanie S. Joy , Lauren M. Aleksunes
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引用次数: 0

摘要

人体血浆中铂金(Pt)未结合部分的定量对于评估化疗药物顺铂的药代动力学非常重要。在这项研究中,我们试图比较使用 Nanosep® 过滤器和 1)传统过滤器(Centrifree®, Centrisart®, Amicon®)或三氯乙酸(TCA)蛋白沉淀法回收未结合铂的情况,以及 2)临床样本中未结合、结合和总铂浓度。对于测试的过滤器,评估了 1)分子量截止值、2)离心力和 3)总铂浓度对人体血浆中铂结合的影响。铂采用电感耦合等离子体质谱法进行定量。在添加了 0.9 μg/mL Pt 的人体血浆中,离心速度越快,未结合铂的百分比越高。相比之下,TCA 蛋白沉淀后未结合铂的百分比最高(42.1%)。当总铂量≤0.9 μg/mL时,各过滤器的未结合铂量(约20-30%)是一致的。相反,当血浆中的铂含量超过 0.9 μg/mL 时,使用超滤时,未结合铂的百分比从 36.5% 增加到 48%,而使用 TCA 沉淀时,未结合铂的百分比则从 63.4% 增加到 79%。在接受含顺铂化疗的患者中,浓度超过 0.9 μg/mL 的未结合铂的比例在 35% 到 90% 之间。此外,血浆中铂的非结合部分与非结合铂浓度(R2 = 0.738)和总铂浓度(R2 = 0.335)相关。总之,本研究证明:1)未结合铂的百分比受体外和临床样本中总铂和未结合铂水平的影响;2)使用 Nanosep® 过滤器进行超滤是量化人体血浆中未结合铂浓度的可行方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Determination of unbound platinum concentrations in human plasma using ultrafiltration and precipitation methods

Quantification of the unbound portion of platinum (Pt) in human plasma is important for assessing the pharmacokinetics of the chemotherapeutic drug cisplatin. In this study, we sought to compare the recovery of unbound Pt using Nanosep® filters to 1) traditional filters (Centrifree®, Centrisart®, Amicon®) or trichloroacetic acid (TCA) protein precipitation, and 2) unbound, bound, and total Pt concentrations in clinical specimens. For the tested filters, the impact of 1) molecular weight cut-offs, 2) centrifugation force, and 3) total Pt concentration on Pt binding in human plasma was evaluated. Pt was quantified using inductively coupled-plasma mass spectrometry. In human plasma spiked with 0.9 μg/mL Pt, the percent of unbound Pt increased at higher centrifugation speeds. By comparison, the percent of unbound Pt was highest (42.1%) following TCA protein precipitation. When total Pt was ≤0.9 μg/mL, unbound Pt (∼20–30%) was consistent across filters. Conversely, when plasma was spiked with Pt exceeding 0.9 μg/mL, the percent of unbound Pt increased from 36.5 to 48% using ultrafiltration, compared to 63.4% to 79% with TCA precipitation. In patients receiving cisplatin-containing chemotherapy, the fraction of unbound Pt at concentrations exceeding 0.9 μg/mL ranged between 35 and 90%. Moreover, the unbound fraction of Pt in plasma correlated with the concentration of unbound (R2 = 0.738) and total Pt (R2 = 0.335). In summary, this study demonstrates that 1) the percent of unbound Pt is influenced by total and unbound Pt levels in vitro and in clinical specimens, and 2) ultrafiltration with Nanosep® filters is a feasible method for quantifying unbound Pt concentrations in human plasma.

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来源期刊
Journal of pharmacological and toxicological methods
Journal of pharmacological and toxicological methods PHARMACOLOGY & PHARMACY-TOXICOLOGY
CiteScore
3.60
自引率
10.50%
发文量
56
审稿时长
26 days
期刊介绍: Journal of Pharmacological and Toxicological Methods publishes original articles on current methods of investigation used in pharmacology and toxicology. Pharmacology and toxicology are defined in the broadest sense, referring to actions of drugs and chemicals on all living systems. With its international editorial board and noted contributors, Journal of Pharmacological and Toxicological Methods is the leading journal devoted exclusively to experimental procedures used by pharmacologists and toxicologists.
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