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Gas chromatographic and mass spectrometric analysis of the products of methylation of sulfonylurea drugs
Author(s) -
Midha K. K.,
Awang D. V. C.,
McGilveray I. J.,
Kleber J.
Publication year - 1976
Publication title -
biomedical mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 0306-042X
DOI - 10.1002/bms.1200030303
Subject(s) - sulfonylurea , chromatography , chemistry , methylation , medicine , biochemistry , insulin , dna
Gas chromatographic analysis of the products of reaction of diazomethane with tolbutamide and chlorpropamide indicates the formation of three compounds in both cases. As expected, N ‐methylation (at sulfonamide nitrogen) is the predominant reaction; minor amounts of O ‐methylated product are also observed. The third product in both cases is the N ‐methylsulfonamide formed by decomposition of the N ‐methylated sulfonylurea during gas chromatography. Electron impact and chemical ionization mass spectrometric analysis, as well as 1 H nuclear magnetic resonance examination of samples collected from gas chromatography, confirm the structural assignments. Additionally, proton magnetic resonance analysis of the crude reaction products established that N ‐methylsulfonamides are not formed in the course of the diazomethane reaction and that the O ‐methylated derivatives are true products of the reaction. The use of a paramagnetic shift reagent allowed direct estimation of the ratios of N ‐ to O ‐methylation, and the demonstration that these ratios are not vitiated during gas chromatographic analysis.