Page 47 - Advances in Forensic Applications of Mass Spectrometry - Jehuda Yinon
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1522_C01.fm  Page 34  Tuesday, December 2, 2003  10:05 AM









                             in plasma. The described and exemplified procedure allows simultaneous,
                             fast, and specific detection of most of the toxicologically relevant drugs
                             (several thousands) in urine samples after therapeutic doses. Therefore, it
                             has proved to be suitable also for screening of abused medicaments in psy-
                             chiatry. After unequivocal identification, quantification of the drugs can be
                             performed, if needed, preferably by GC/MS or LC/MS.

                             1.4.2.3  General Screening Procedures for Simultaneous
                                      Detection of Several Classes of Acidic Drugs
                                      in Urine after Extractive Methylation
                             A comprehensive GC/MS screening procedure for the detection of acidic
                             drugs, poisons, and/or their metabolites in urine after extractive methylation
                             was developed. 65–69  The analytes were separated by capillary GC and identi-
                             fied by computerized MS in the full scan mode. As already described above,
                             the possible presence of acidic drugs and/or their metabolites could be indi-
                             cated using mass chromatography with selective ions followed by peak iden-
                             tification using library search. 92,94
                                This STA method allows the detection in urine of most of the  ACE
                             inhibitors and AT  blockers,  coumarin anticoagulants of the first genera-
                                                      66
                                             1
                                                                       67
                                                                                    68
                             tion,  dihyropyridine calcium channel blockers,  barbiturates,  diuretics, 317
                                 65
                                                                               32
                             antidiabetics of the sulfonylurea type (sulfonamide part),  NSAIDs,  and of
                                                                                        69
                             various other acidic compounds.  At least the higher dosed drugs could also
                                                         32
                             be detected in plasma samples after extractive methylation.
                             1.5 Conclusions and Perspectives
                             In the last few  years, many papers have been published concerning GC/MS
                             screening in body fluids for unknown drugs and their metabolites relevant
                             to clinical toxicology, forensic toxicology, and doping control. They either
                             describe procedures for confirmation of chromatographic or immunological
                             results or for STA. Confirmation  is usually performed in the SIM mode
                             because only particular compounds have to be identified. GC/MS is today
                             the method of choice for STA in clinical and forensic toxicology as well as
                             in doping control. If the drug is unknown, full scan mode is the method of
                             choice, since comparison of the full mass spectra with reference spectra is
                             necessary and provides best specificity. The screening can be performed
                             using mass chromatography followed by library search. Besides common
                                                            92
                             toxicological mass spectral libraries  very large mass spectra collections with
                             more than 200,000 entries 95,96  can also be used. Quantification in the SIM
                             mode provides very good precision especially using stable isotopes as internal
                             standards. However, they are commercially available for only a few drugs.


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