Positive ion EI mass spectra of 2,3,5-trisubstituted-1,5-benzothiazepines, diltiazem, clentiazem and their fat-soluble metabolites.

Abstract

Diltiazem, clentiazem and their acidic and basic metabolites extractable with tert-butyl methyl ether, which are all 2,3,5-trisubstituted-1,5-benzothiazepines, were analysed by positive ion electron ionization (PIEI) mass spectrometry, and the structures of fragment ions and their fragmentation pathways were investigated. In all the mass spectra of these compounds, b1 ions ([R1 - CH = CH - OR2]+) or b2 ions ([R1 - CH = CH - OH]+, b1 - CH2CO; R2 = COCH3) were seen as the base peaks or one of the major peaks (R1 and OR2 are the substituents at position 2 and 3, respectively). These spectra varied greatly with the nature of the side-chain at position 5: in the spectra of compounds with a 5-(2-dimethylamino) ethyl group, the a1 ion, [CH2 = N(CH3)2]+, was the base peak ion; in those with a 5-(2-monomethyl-amino)ethyl group (trifluoroacetyl(TFA)-derivatives), no a1 ion peak was seen, but the a3 ion, [CH2CH2NCH3TFA]+, was one of the major peaks; in those of the derivatives bearing a 5-(2-amino) ethyl or -carboxymethyl group, no peaks indicating the structures of the side-chain group at position 5 could be seen. GC-mass chromatography using fragment ions such as the a1, a3, b1 and b2 ions enables detection of the unchanged drug and most of its metabolites obtained by extraction with organic solvents under acidic or basic conditions followed by derivatization.