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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Specific determination of pentamethylmelamine and its demethylated metabolites in human plasma by high pressure liquid chromatography.

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.[1]

References

  1. Specific determination of pentamethylmelamine and its demethylated metabolites in human plasma by high pressure liquid chromatography. Leyland-Jones, B.R., Deesen, P.E., Casper, E.S., Young, C.W. Therapeutic drug monitoring. (1982) [Pubmed]
 
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