Leyland-Jones B R, Deesen P E, Casper E S, Young C W
Ther Drug Monit. 1982;4(2):185-90. doi: 10.1097/00007691-198206000-00005.
Pentamethylmelamine (PMM) and its demethylated metabolites tetra-N2246, tri-N246 and tri-N224 have comparable relative antitumor potencies in animal systems. We have developed a sensitive and specific high pressure liquid chromatography (HPLC) assay for these compounds in the plasma of patients receiving pentamethylmelamine, a cytotoxic S-triazine derivative now undergoing clinical trials. The method involves analysis of an ethyl acetate extract of plasma by a high pressure liquid chromatograph containing a reverse-phase column and ultraviolet detection at 240 nm. The mobile phase is acetonitrile and KH2PO4 buffer (pH 5.5); gradient elution over 25 min yields relative retention times to hexamethylmelamine as internal standard of 0.36, 0.40, 0.54 and 0.70 for tri-N246, tri-N224, tetra-N2246 and PMM. The lower limit of sensitivity for each is 300 ng/ml. Pharmacokinetic studies on four patients receiving a 24-h infusion of PMM (doses 900-3000 mg/m2) showed a mean terminal half-life of PMM of 101 +/- 28 (SD) min, a mean volume of distribution of 2036 +/- 75 ml/kg, and a metabolic clearance rate of 14.2 +/- 3.7 (ml/min)/kg. Mean areas under the plasma-vs-time curves of tri-N246, tri-N224 and tetra-N2246 were 126%, 41% and 56% of PPM, demonstrating extensive formation of these metabolites in man.
五甲基三聚氰胺（PMM）及其去甲基化代谢产物四 - N2246、三 - N246和三 - N224在动物系统中具有相当的相对抗肿瘤效力。我们已开发出一种灵敏且特异的高压液相色谱（HPLC）分析法，用于测定接受五甲基三聚氰胺治疗的患者血浆中的这些化合物。五甲基三聚氰胺是一种细胞毒性S - 三嗪衍生物，目前正在进行临床试验。该方法包括通过配备反相柱和240nm紫外检测的高压液相色谱仪分析血浆的乙酸乙酯提取物。流动相为乙腈和KH2PO4缓冲液（pH 5.5）；25分钟的梯度洗脱产生相对于作为内标的六甲基三聚氰胺的相对保留时间，三 - N246、三 - N224、四 - N2246和PMM分别为0.36、0.40、0.54和0.70。每种化合物的最低检测限为300ng/ml。对四名接受24小时PMM输注（剂量900 - 3000mg/m2）的患者进行的药代动力学研究表明，PMM的平均终末半衰期为101±28（SD）分钟，平均分布容积为2036±75ml/kg，代谢清除率为14.2±3.7（ml/分钟）/kg。三 - N246、三 - N224和四 - N2246的血浆 - 时间曲线下平均面积分别为PMM的126%、41%和56%，表明这些代谢产物在人体内大量形成。
