Positive and negative ion mass spectrometry of ten xanthine derivatives and their rapid clean-up with Sep-Pak C 18 cartridges from biological samples

Abstract

Positive ion electron impact (PIEI), positive ion chemical ionization (PICI) and negative ion chemical ionization (NICI) mass spectra are presented for ten xanthine derivatives; and each fragmentation pathway has been analyzed. In the PIEI mode, molecular ions were generall intense and constituted base peaks in five compounds. Peaks at m z 42 (NCO) appeared in all compounds; fragment cations at m z 55, 68 (or 67) and 82 were observed in many compounds. In the PICI mode, all drugs showed intense [M+H] + quasi-molecular peaks together with small peaks at m z M+C 2H 5 and M+C 3H 5; fragment peaks at m z 44, 58, 72 and/or 84 (or 86) were also observed. In the NICI mode, [M−H] − quasi-molecular peaks appeared in nine compounds and constituted base peaks in five compounds; adduct anions at m z M+32 and/or M+C 3H 7, and fragment anions at m z 42, 165 and/or 179 were also observed in many compounds. Detection limits for total ion monitoring of the drugs in the PIEI, PICI and NICI modes were 2.2–10 ng, 11–28 ng and 7.8–14 ng on column, respectively. Xanthine derivatives present in human plasma or urine could be rapidly extracted by use of Sep-Pak C 18 cartridges with chloroform/methanol as elution solvent; recovery of the drugs from the plasma and urine was > 75%. They were also detected by capillary gas chromatography (GC) with both flame ionization detection (FID); their limits were 1.6–8.3 ng on column.