Positive- and negative-ion mass spectrometry of diphenylmethane antihistaminics and their analogues and rapid clean-up of them from biological samples

Abstract

Positive-ion electron impact (PIEI), positive-ion chemical ionization (PICI) and negativeion chemical ionization (NICI) mass spectra are presented for 15 compounds of diphenylmethane antihistaminics and their analogues, and each fragmentation pathway was analyzed. In the PIEI mode, molecular peaks were very small or missing for most compounds. Peaks at m z 58, due to a dimethylaminomethyl group liberated, constituted base peaks in five compounds. Peaks at m z 165 and/or 167, due to diaromatic rings plus a methyl group, appeared in most compounds. In the PICI mode, peaks due to M + H and M + C 2H 5 appeared in all compounds. Peaks due to diaromatic rings plus a methyl or ethyl group constituted base peaks in five compounds, which had an ether bond in their structures. In the NICI mode, anions at m z M-H appeared in most compounds. Peaks at m z 35 were observed for compounds having a chlorine group in their structures. Detection limits for total ion monitoring of these compounds were 20–50 ng on column in the PIEI mode, 100–200 ng in the PICI mode and 500–1000 ng in the NICI mode. A rapid and simple clean-up procedure of these drugs with use of Sep-Pak C 18 cartridges is also presented. The drugs could be detected by gas chromatography with DB-1 and DB-17 capillary columns with satisfactory separation from impurities in their underivatized forms. The recovery of the drugs, which had been added to whole blood and urine, was more than 60% except for meclizine.