Bis-pentafluorobenzyl derivatives of N-acetyl-l-methionine and N-acetyl-l-selenomethionine for the quantitative determination in human plasma by gas chromatography–negative ion chemical ionisation mass spectrometry

Abstract

Targeted anti-cancer combination therapy with infusion of N-acetyl-l-methionine (NALM) and N-acetyl-l-selenomethionine (NASeLM) shows promising results in cancer treatment. Selenium has been recognised as a valuable additive in cancer therapeutics due to its ability to minimise side effects of chemotherapy and its role in cancer prevention and therapy. Due to the promising results of this new therapeutic approach evaluation of pharmacokinetic data for NALM and NASeLM is of ultimate importance. We have therefore elaborated a method for the quantitative measurement of these compounds in human plasma based on GC–negative ion chemical ionisation-MS. The derivatisation sequence elaborated can be regarded as a novel strategy for the chemical modification of delicate sulphur- and selenium-containing compounds, and underlines the enhanced reactivity of selenium-analogues of sulphur-containing amino acids. The target compounds were extracted from plasma with ethyl acetate and converted to the S/Se-pentafluorobenzyl-homocysteine pentafluorobenzyl ester derivative. Reaction conditions were optimised for derivative yield. Calibration graphs were established in the range of 2.938–481.105ng/0.5mL plasma (NALM) and 0.233–59.543ng/0.5mL plasma (NASeLM). Accuracy, precision and stability data were elaborated. The method was applied to pharmacokinetic profiling of the compounds after infusion into human volunteers.