A HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY WITH IMPROVED SELECTIVITY FOR CISPLATIN AND ACTIVE PLATINUM(II) COMPLEXES IN PLASMA ULTRAFILTRATE
A HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY WITH IMPROVED SELECTIVITY FOR CISPLATIN AND ACTIVE PLATINUM(II) COMPLEXES IN PLASMA ULTRAFILTRATE
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DOI：
10.1016/0003-2697(84)90556-6
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发表时间：
1984-01-01
影响因子：
2.9
通讯作者：
HOWELL, SB
中科院分区：
文献类型：
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作者：
ANDREWS, PA;WUNG, WE;HOWELL, SB
用二乙基二硫代氨基甲酸钠（DDTC）衍生后，通过氯化镍内标物定量测定血浆超滤液中的顺式二氨二氯铂（II）（DDP）。在C18径向压缩柱上，用反相高效液相色谱法分离了Pt（DDTC）2和Ni（DDTC）2的氯仿萃取物。用甲醇/水（4/1）洗脱，流速1.5ml/min，检测波长254 nm。超滤液中的灵敏度极限为0.1 μ g/ml DDP。该分析方法通过与一式两份样品的石墨炉原子吸收分光光度法测定进行比较进行了验证。显然存在对DDTC衍生化具有抗性的超滤Pt组分。有证据表明，这种成分，推测铂（II）与内源性小分子复合，是非细胞毒性的，因此，这种方法可能是选择性的“活性铂（II）”。该方法提供了一个优势，超过原子吸收法测定总铂超滤液，不区分活性和非活性形式，并超过离线FAA检测母DDP的HPLC洗脱液，忽略了其他活性形式。使用这种技术，DDTC反应性Pt（II）的药代动力学测定后，无论是静脉输注或输注DDP到卵巢癌患者的腹膜腔中的人类。
cis-Diamminedichloroplatinum(II) (DDP) was measured in plasma ultrafiltrate following derivatization with sodium diethyldithiocarbamate (DDTC) by quantitation against a nickel chloride internal standard. A chloroform extract containing the Pt(DDTC)2 and Ni(DDTC)2 complexes was separated by reversed-phase high-performance liquid chromatography HPLC on a C18 radial compression column. The complex was eluted with methanol/water, 4/1, at a flow rate of 1.5 ml/min, and was detected at 254 nm. The limit of sensitivity was 0.1 .mu.g/ml DDP in the ultrafiltrate. This analytical approach was validated by comparison to graphite furnace atomic absorption spectrophotometric determinations of duplicate samples. There was clearly a component of the ultrafilterable-Pt present that was resistant to derivatization by DDTC. Evidence is presented that this component, presumably Pt(II) complexed with endogenous small molecules, is non-cytotoxic and, hence, that this method may be selective for "active Pt(II)". This method offers an advantage over atomic absorption determination of total Pt in ultrafiltrate which does not discriminate between active and inactive forms, and over off-line FAA detection of parent DDP in HPLC eluates which ignores other active forms. Using this technique the pharmacokinetics of DDTC-reactive Pt(II) was measured in humans after either i.v. infusion or infusion of DDP into the peritoneal cavity of patients with ovarian carcinoma.