Page 114 - Advances in Forensic Applications of Mass Spectrometry - Jehuda Yinon

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ions of all drugs and the internal standard were monitored by ESI/MS. The
LODs were 1 to 5 mg/l, LOQ was 10 mg/l. LC/MS methods for fluoxetine and
its metabolite were frequently published. A fast ESI/LC/MS/MS method for
determination of fluoxetine and norfluoxetine was developed by Sutherland
153
et al. The drugs and internal standard (doxepin) were extracted from
plasma with hexane–isoamylalcohol (98:2) and the aqueous phase was frozen
and discarded. The organic phase was back-extracted with 2% formic acid;
the aqueous phase was frozen and, after discarding of the hexane layer,
thawed, and injected into LC/MS. The total chromatographic run time was
2.6 min. The transition of protonated quasi-molecular ions of drugs to prod-
uct ions was monitored. The LOQ was 0.15 mg/l for both compounds. In a
154
procedure published by Shen et al., fluoxetine was extracted with solvent
in 96-well plates and enantiomers of the drug were separated on a vancomy-
cin column. The detection was done with an APCI/MS/MS in MRM mode.
155
The limit of quantitation was 2 mg/l. Li et al. published a highly sensitive
LC/ESI/MS/MS procedure for the determination of fluoxetine and norfluox-
etine in human plasma. The drugs were extracted from plasma with solvent
and separated within 5 min. The LOD of 0.1 mg/l was reported at a sample
size of 0.2 ml.
Olanzapine, a thienobenzodiazepine, is an antipsychotic agent used
broadly for the acute treatment and maintenance of schizophrenia. Due to
the concentration-related response and toxicity, therapeutic monitoring of
this drug is indicated. Berna et al. 156,157 published two procedures for LC-
ESI/APCI-MS-MS determination of olanzapine in plasma. The drug was
extracted with SPE cartridges or with organic solvent mixture in single or
96-well format. The LOQ was 0.25 mg/l. Bogusz et al. applied LC/APCI/MS
158
for determination of olanzapine in serum. SPE extraction on C18 cartridges
was applied. The LOQ was 1 mg/l. In full-scan LC/MS a postulated olanzap-
ine-10-N-glucuronide was found in urine. Aravagiri and Marder 159 applied
LC/ESI/MS/MS for therapeutic drug monitoring of clozapine, clozapine-N-
oxide, and norclozapine in the serum of schizophrenic patients. The drugs
were isolated with solvent extraction and separated on ODS column. The
transitions of protonated quasi-molecular ions to single fragments were
monitored. An LOQ of 1 mg/l for all substances was reported. The same
authors used LC/ESI/MS/MS for the determination of risperidone and
160
9-hydroxyrisperidone in plasma. Solvent extraction and separation on a
phenyl-hexyl column was applied. The LOQ was 0.1 mg/l. Venlafaxine, a
phenethylamine antidepressant, as well as its O-desmethylated metabolite
were determined in postmortem blood and tissues in 12 cases of fatal ven-
lafaxine poisoning. The drug was extracted with butyl chloride and deter-
161
mined by LC/ESI/MS in a positive ionization mode. In all cases, various other
psychotropic drugs and alcohol were also detected.

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