Shiba D A, Weinkam R J
J Chromatogr. 1982 May 14;229(2):397-407. doi: 10.1016/s0378-4347(00)84282-6.
Quantitative analytical methods are described for the analysis of the anticancer drug procarbazine and eight known metabolites including those known to have cytotoxic activity. A direct sample insertion mass spectrometric assay for procarbazine and the urinary excretion product, N-isopropyl-terephthalamic acid, has been developed. This method employs stable isotope labeled variants in a procedure that minimizes analytical errors that may be encountered in the quantitation of the chemically unstable parent drug. a liquid chromatographic method is described for the analysis of seven known procarbazine metabolites. Use of these methods is demonstrated by the analysis of procarbazine metabolism during incubation in a 9000-g rat liver homogenate preparation. Procarbazine disappearance and metabolite appearance are also monitored in rat plasma following intraperitoneal administration of a 150 mg/kg bolus dose. Applications to patient pharmacokinetics is demonstrated using the liquid chromatographic assay to follow the appearance of active procarbazine metabolites on the first and fourteenth day of an oral 250 mg/kg/day course of therapy of a patient being treated for cancer.
描述了定量分析方法，用于分析抗癌药丙卡巴肼及其8种已知代谢物，包括那些已知具有细胞毒性活性的代谢物。已开发出一种用于丙卡巴肼和尿液排泄产物N - 异丙基对苯二甲酰胺酸的直接进样质谱分析法。该方法在一个程序中采用稳定同位素标记的变体，最大限度地减少了在定量化学性质不稳定的母体药物时可能遇到的分析误差。描述了一种液相色谱法，用于分析7种已知的丙卡巴肼代谢物。通过在9000g大鼠肝脏匀浆制剂中孵育期间分析丙卡巴肼代谢情况，证明了这些方法的实用性。在腹腔注射150mg/kg大剂量后，还对大鼠血浆中的丙卡巴肼消失和代谢物出现情况进行了监测。使用液相色谱分析法跟踪一名癌症患者口服250mg/kg/天疗程治疗的第一天和第十四天活性丙卡巴肼代谢物的出现情况，证明了该方法在患者药代动力学中的应用。
