Substance identification: the weak link in analytical toxicology.

Although substance identification is a key factor in analytical toxicology, it is amazing that the subject is receiving very limited and often inappropriate attention. With regard to the latter, a "confirmation" approach is usually chosen, which does not yield unambiguous identification. Moreover, the criteria for establishing a "positive match" leave much to be desired. These observations are corroborated when comparing some recent guidelines for qualitative analysis (issued for various forensic areas by SOFT/AAFS, NCCLS, NLCP, WADA and EU). Apart from showing substantial differences between them on pivotal issues, the guidelines contain various elements that appear scientifically incorrect and/or legally untenable. Also, the guidelines focus primarily on mass spectrometry (MS) and pay little or no attention to other identification possibilities (such as chromatographic techniques, either in combination with MS or as stand-alone techniques. Moreover, they do not offer alternatives in situations where access to MS is not available. One must conclude, therefore, that substance identification is a neglected and misunderstood domain in analytical toxicology. Rapid and concerted actions are needed to: (1) improve the general knowledge; (2) to define uniform strategies in the analytical approach and in the interpretation of the results; and (3) to set up and maintain suitable banks of reference substances and computerized data bases to allow unambiguous identification.

Polymorphic drug metabolism (CYP2D6) and utilisation of psychotropic drugs in hospitalised psychiatric patients: a retrospective study.

AIM: The aim of the current retrospective study was to assess the influence of polymorphic drug metabolism as assessed by genotyping, on the on the utilisation of psychotropic drugs in hospitalised psychiatric patients. The utilisation of psychotropic drugs was assessed using pharmacy records with emphasis on the number of prescriptions and prescriptions for possible side effects. METHODS: CYP2D6 genotype was assessed in 241 psychiatric patients by investigation for the five most common allelic variants ( CYP2D6*3, *4, *6, *7, *8) and the presence of gene duplication using allele-specific polymerase chain reaction. Data concerning the pharmacotherapy of the patients were retrieved from the pharmacy information system. Data was analysed on differences observed in pharmacy records concerning the different metabolic classes: ultra rapid metabolisers (UMs), extensive metabolisers (EMs) and poor metabolisers (PMs). RESULTS: For CYP2D6, 2.5% was UM (95% CI: 0.5-4.5%, n=6) and 8.3% was PM (95% CI: 4.8-11.8%, n=20). Drugs metabolised by CYP2D6 were less frequently prescribed in PMs than EMs (21.1% vs 33.6%, P=0.023). The average duration of prescriptions was significantly lower in PMs than EMs (54 days vs 106 days, P=0.010). Between UMs and EMs, no significant differences were found, although a similar tendency was observed. With regard to dose, no consistent differences were observed between the CYP2D6 genotype classes. Drugs against Parkinsonian-like side effects were given twice as frequently in PMs as EMs (6.9% vs 3.4%, P=0.045). CONCLUSIONS: Patients with impaired CYP2D6 metabolism received fewer CYP2D6 drugs. PMs were more prone to Parkinsonian-like side effects as evidenced by more prescriptions for drugs combating these side effects. Dose titrations were not often used to compensate for genetic polymorphisms. Pharmacy records might be a useful tool to detect differences related to polymorphic metabolism.

Spherical molecularly imprinted polymer particles: a promising tool for molecular recognition in capillary electrokinetic separations.

Spherical molecularly imprinted polymer particles obtained via precipitation polymerization, were introduced as a pseudostationary phase in capillary electrophoresis (CE) to study molecular recognition. Analyses were performed via a partial filling technique using (+)-ephedrine-imprinted microspheres (100-200 nm) which were polymerized from methacrylic acid and 1,1,1-Tris(hydroxymethyl)propanetrimethacrylate using acetonitrile as the solvent. The influence of pH and the modifier content on the separation was investigated. A 0.1% w/v suspension in an aqueous 10 mM phosphate buffer (pH 2.5 with 40% acetonitrile) was hydrodynamically injected into the CE system (80% of the effective capillary length) and led to full baseline separation of racemic ephedrine within 10 min.

Interlaboratory reproducibility of mobility parameters in capillary electrophoresis for substance identification in systematic toxicological analysis.

An interlaboratory pilot study was performed to determine the reproducibility of mobility parameters in capillary zone electrophoresis (CZE) and micellar electrokinetic chromatography (MEKC). The study was performed by an intended small number of laboratories (three) that used different brands of instruments (two). The effective mobility was corrected using standards by a method that was recently introduced to obtain a more reproducible migration parameter. A test set of 20 acidic test compounds and 5 reference compounds were analyzed during five days in each laboratory using CZE and MEKC. Buffers used consisted of 90 mM borate set at pH 8.4 (CZE) and 20 mM phosphate, 50 mM sodium dodecyl sulfate set at pH 7.5 (MEKC). Analyses were carried out using fused-silica capillaries at an electric field strength of either 52.6 kV/m or 37.5 kV/m. The interlaboratory reproducibility (mean RSD) of the effective mobility was 3.0% for CZE and 6.7% for MEKC. After applying the correction method, these values became 3.0% for CZE and 3.3% for MEKC, which is adequate for systematic toxicological analysis (STA) applications. A significant improvement of reproducibility for the calculated corrected effective mobility mu(eff)c was observed when variations are high. Therefore, it is recommended to use the correction method in interlaboratory situations, especially when instruments and capillaries from different manufacturers are used.