A Comparison of the Quantitative Methods for the Analysis of the Platinum-Containing Anticancer Drug {cis-[Amminedichloro(2-methylpyridine)]- platinum(II)} (ZD0473) by HPLC Coupled to Either a

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• 作者：Christopher J. Smith ; Ian D. Wilson ; Fadi Abou-Shakra ; Richard Payne ; Tony C. Parry ; Peta Sinclair ; and David W. Roberts
• 刊名：Analytical Chemistry
• 出版年：2003
• 出版时间：March 15, 2003
• 年：2003
• 卷：75
• 期：6
• 页码：1463 - 1469
• 全文大小：97K
• 年卷期：v.75,no.6(March 15, 2003)
• ISSN：1520-6882

文摘

The use of high performance liquid chromatographycoupled with inductively coupled plasma mass spectrometry (HPLC-ICPMS) as means for the quantitative determination of ZD0473, a platinum anticancer drug, and itsrelated biologically active "aqua" compounds in biofluidsamples is described. The performance of the resultingHPLC-ICPMS method was compared with that of aconventional HPLC-triple quadrupole mass spectrometer-based (HPLC-MS/MS) system for properties such aslimit of detection, linearity, and reproducibility usingspiked samples. The methods were then applied to thedetermination of plasma ultrafitrate concentrations ofZD0473 in dog plasma samples obtained following intravenous and oral administration at 0.5 and 6 mg/kg,respectively. These experiments showed that both methods were capable of providing accurate and precise resultsbut that the HPLC-ICPMS method had advantages ofextended linear range and superior sensitivity, providinga limit of quantification of 0.1 ng/mL for ZD0473, ascompared to 5 ng/mL using the current HPLC-MS/MSmethod. In addition, by using a single combined HPLC-ICPMS/MS/MS system, it was possible to determine therelative MS/MS response of the aqua compounds for thefirst time.