Comprehensive identification of active compounds in tablets by flow-injection data-dependent tandem mass spectrometry combined with library search

Abstract 

A convenient mass spectrometric approach for the identification of toxicologically relevant compounds in tablets and tablet residues is presented. For comprehensive forensic-toxicological analysis electrospray ionization mass spectrometry was accomplished in positive as well as in negative ion mode on a quadrupole–quadrupole–time-of-flight instrument. Dissolved samples were introduced into the mass spectrometer by flow-injection. Mass spectra as well as tandem mass spectra were acquired. A data-dependent acquisition strategy was used to switch between the mass spectrometric modes. Identification was accomplished via search within a tandem mass spectral library. The applied database contained 8252 spectra collected from 836 compounds in positive ion mode as well as 1023 spectra collected from 103 compounds in negative ion mode. A total of 22 casework samples collected during autopsies from mouth, oesophagus or gastric contents, seized by the police, or found with patients at hospital were screened. Twelve samples contained compounds only detectable in positive ion mode (sildenafil, dihydrocodeine, diphenhydramine, oxprenolol, N-methyl-3,4-methylenedioxyamphetamine, morphine, amphetamine, caffeine, pemoline, orphenadrine, m-chlorphenylpiperazine and tramadol), six samples contained species exclusively detectable in negative ion mode (salicylic acid, acetylsalicylic acid, ibuprofen, ketorolac, valproic acid and phenobarbital), and three samples contained diclofenac detectable in both ionization polarities. One sample did not contain any compound amenable to mass spectrometric analysis. For verification all samples were additionally analyzed by GC/MS. Both methods revealed identical results for all but one sample. The beta-adrenergic blocker oxprenolol was exclusively detected by the flow-injection method.

Keywords: General unknown screening, Electrospray ionization, Mass spectrometry, Tandem mass spectrometry, Mass spectral library, Flow-injection