Determination of metabolites of a novel platinum anticancer drug JM216 in human plasma ultrafiltrates

被引：34

作者：

Poon, GK ^{[1
]}

Mistry, P ^{[1
]}

Raynaud, FI ^{[1
]}

Harrap, KR ^{[1
]}

Murrer, BA ^{[1
]}

Barnard, CFJ ^{[1
]}

机构：

[1] JOHNSON MATTHEY TECHNOL CTR,READING RG4 9NH,BERKS,ENGLAND

来源：

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS | 1995年 / 13卷 / 12期

关键词：

platinum anticancer drug; metabolites; human plasma ultrafiltrate; electrospray ionisation mass spectrometry;

D O I：

10.1016/0731-7085(95)01571-X

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

The present study describes the application of on-line liquid chromatography-electrospray ionisation in conjunction with a high resolution magnetic sector mass spectrometer to identify metabolites of a platinum(IV) anticancer drug JM216 [bis(acetato)amminedichloro(cyclohexylamine)platinum(IV)] in human plasma. Four metabolites were identified following incubation of JM216 in human plasma: JM118 [amminedichlorocyclohexylamineplatinum(II)], a platinum(II) complex; JM383 [bis(acetato)amminedihydroxo(cyclohexylamine)platinum(IV)]; JM518 [bis(acetato)amminechloro(cyclohexylamine)hydroxoplatinum(IV)I] and its isomer JM559. The platinum complexes mass spectra were dominated by the natriated [M + Na](+) ion. Elemental compositions of these natriated ions were confirmed by accurate mass measurement on a magnetic sector mass spectrometer in the course of LC/MS analysis. This study demonstrates the capability of direct LC-ESI/MS with accurate mass measurement for analysis of platinum complexes in biological samples. Our results suggest that LC-ESI/MS is a powerful technique for structure elucidation of novel metabolites, and could make valuable contributions to drug metabolism research.

引用

页码：1493 / 1498

页数：6

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