Page 115 - Advances in Forensic Applications of Mass Spectrometry - Jehuda Yinon

1522_C02.fm Page 100 Wednesday, November 12, 2003 9:36 AM

2.4.5 Other Therapeutic Compounds of Forensic Relevance

Methylphenidate is a central stimulant with a history of abuse which is used
for the treatment of narcolepsy. The drug has two chiral centers and is
marketed as a racemic mixture, whereas d-threo-methylphenidate is pharma-
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cologically more active than the l-isomer. Ramos et al. described an
LC/APCI/MS/MS procedure for determination of methylphenidate enanti-
omers in plasma. A vancomycin-based Chirobiotic V column was used for
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separation. The LOQ was 87 ng/l. In the next study, Ramos et al. developed
an LC/APCI/MS/MS method for the determination of racemic methylpheni-
date. Alkaline cyclohexane extraction in a 96-well plate format was utilized.
The drug was separated on C18 column using switching valve, diverting first
part of eluent to waste. Total run time was 3 min, a LOQ of 50 ng/l plasma
was reported.
Scopolamine and the internal standard atropine were extracted from 0.2
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ml serum with Oasis HLB cartridges in an automated procedure. The drugs
were separated on a C18 column in gradient elution on a mobile phase
consisting of ACN, ammonium acetate, and formic acid. The detection was
done with ESI/MS/MS (positive ions). Protonated quasi-molecular ions of
scopolamine and atropine were used as parent ions and two product ions for
each drug were monitored. The method was applied for pharmacokinetic
studies with a LOQ of 20 ng/l serum.
Nicotine and its seven metabolites were determined in urine by
LC/ESI/MS/MS after enzymatic hydrolysis and solvent extraction. For quan-
13
titation, deuterated or C-labeled analogs were used for each compound.
The LODs ranged from 5 to 38 ng/l. The most dominant metabolite was
identified as 3-OH-cotinine. 165
Sildenafil became an extremely popular drug and at least 100 million
tablets have been prescribed worldwide. It may cause not only several adverse
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effects but also life-threatening cardiac failure. Weinmann et al. described
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postmortem detection and identification of sildenafil (Viagra) and its metab-
olites by LC/ESI/MS and LC/ESI/MS/MS. The drug and three metabolites
were isolated from the urine and organs of a highly putrefied body of an 80-
year-old man who died due to coronary sclerosis. Analytical results were
compared with experimental data obtained from a volunteer who ingested
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25 mg sildenafil. French authors used LC/ESI/MS for the determination of
sildenafil and verapamil in blood, organs, and hair of a 43-year-old man who
was found dead after sexual relations with a prostitute. The deceased had a
history of cardiovascular disease and erectile dysfunction. Sildenafil may be
also used as a doping substance for racehorses due to its protective action
against exercise-induced pulmonary hemorrhage. Rudy et al. presented an
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LC/ESI/MS/MS method for identification of sildenafil and metabolites in
equine plasma and urine. A liquid/liquid-alkaline extraction was applied,

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