Berger B J, Suskin M, Dai W W, Cerami A, Ulrich P
The Picower Institute for Medical Research, Manhasset, NY 11030, USA.
J Chromatogr B Biomed Sci Appl. 1997 Apr 11;691(2):433-40. doi: 10.1016/s0378-4347(96)00478-1.
A method utilising solid-phase extraction followed by high-performance liquid chromatography has been developed to quantify novel arylene bis(methylketone) chemotherapeutics present in biological samples. The samples are extracted over cyanopropylsilane solid-phase extraction cartridges using 10 mM heptanesulfonate-10 mM tetramethylammonium chloride-4.2 mM H3PO4-95% CH3CN as the eluent. Analytical chromatography utilises a diisopropyl-C8 reversed-phase column and a 7.5-45% CH3CN gradient in 10 mM heptanesulfonate-10 mM tetramethylammonium chloride-4.2 mM H3PO4-H2O. Detection was by ultraviolet spectrophotometry at 300 or 240 nm. The linear response of the assay was found to extend from at least 100 microg/ml down to 97.66 ng/ml for a 100 microl injection. The assay system was utilised to determine the plasma kinetics of the compounds in mice, where all the drugs were found to display rapid absorption and elimination following intraperitoneal dosing. In vitro and in vivo studies of metabolism demonstrated that each of the compounds produced several metabolites, and that this conversion could be extensive in vivo.
已开发出一种利用固相萃取随后进行高效液相色谱分析的方法，用于定量生物样品中存在的新型亚芳基双（甲基酮）化疗药物。使用10 mM庚烷磺酸盐-10 mM四甲基氯化铵-4.2 mM磷酸-95%乙腈作为洗脱剂，在氰丙基硅烷固相萃取柱上对样品进行萃取。分析色谱使用二异丙基-C8反相柱，并在10 mM庚烷磺酸盐-10 mM四甲基氯化铵-4.2 mM磷酸-水体系中采用7.5-45%乙腈梯度。通过在300或240 nm处的紫外分光光度法进行检测。对于100 μl进样，该测定的线性响应范围被发现至少从100 μg/ml延伸至97.66 ng/ml。该测定系统被用于确定化合物在小鼠体内的血浆动力学，发现所有药物在腹腔给药后均表现出快速吸收和消除。代谢的体外和体内研究表明，每种化合物都会产生几种代谢物，并且这种转化在体内可能很广泛。
