Methadone and impairment in apprehended drivers.

AIMS: According to Norwegian guidelines, patients who are in opioid-assisted rehabilitation programmes are permitted to drive a motor vehicle provided that certain requirements are met. The purpose of this study was to investigate apprehended drivers who had methadone in their blood at the time of apprehension and, further, the relationship between blood methadone concentration and impairment as measured by the clinical test of impairment (CTI). METHODS: The division of Forensic Toxicology and Drug Abuse (DFTDA) at the Norwegian Institute of Public Heath analyses blood samples from all drivers suspected of driving under the influence of drugs nation-wide. Cases with positive results for methadone in blood were collected over the period 2001-2006. RESULTS: A total of 635 drivers with methadone found in their blood samples were identified. The majority of drivers were men (>80%), aged between 30 and 40 years. Methadone was the only psychoactive drug detected in blood in only 10 cases. Benzodiazepines were a frequent finding (in approximately 90% of cases). A significant difference in blood methadone concentration was found between cases where only methadone was detected [median 0.46 mg/l (range 0.19-0.65)] and cases where methadone was detected in combination with other psychoactive drugs [median 0.28 mg/l (range 0.06-1.24)]. A CTI had been carried out, in conjunction with blood sampling, in 577 of the cases. A concentration-impairment relationship was not seen for methadone in these cases. CONCLUSIONS: Cases of driving impairment involving methadone alone were very rare, with combination use most frequent. No correlation between methadone concentration and impairment as judged by the CTI was seen either for these cases or for the material as a whole.

Simultaneous determination of 6 beta-blockers, 3 calcium-channel antagonists, 4 angiotensin-II antagonists and 1 antiarrhythmic drug in post-mortem whole blood by automated solid phase extraction and liquid chromatography mass spectrometry. Method development and robustness testing by experimental design.

A method for the simultaneous determination of the beta-blockers atenolol, sotalol, metoprolol, bisoprolol, propranolol and carvedilol, the calcium-channel antagonists diltiazem, amlodipine and verapamil, the angiotensin-II antagonists losartan, irbesartan, valsartan and telmisartan, and the antiarrhythmic drug flecainide, in whole blood samples from forensic autopsies was developed. Sample clean-up was achieved by precipitation and solid phase extraction (SPE) with a mixed-mode column. Quantification was performed by reversed phase high performance liquid chromatography with positive electrospray ionization mass spectrometric detection (HPLC-MS). The method has been developed and robustness tested by systematically searching for satisfactory conditions using experimental designs including factorial and response surface designs. With the exception of amlodipine, the concentration limit of quantification (cLOQ) covered low therapeutic concentration levels for all the compounds. Within assay precisions and accuracies (bias) were 3.4-21% RSD and from -24 to 21% for the concentration range 1.00-5.00 microM, respectively. Between assay precisions were 4.4-28% RSD for the concentration range from 0.1 to 5 microM and recoveries varied from 9 to 103%. The method is used for determination of cardiovascular drugs in post-mortem whole blood samples from forensic autopsy cases.

Three-phase liquid-phase microextraction of weakly basic drugs from whole blood.

The behaviour of weak basic analytes in liquid-phase microextraction (LPME) and the optimisation of parameters in whole blood are described. Benzodiazepines and non-benzodiazepine drugs were chosen as model substances. Liquid-phase microextraction based on disposable polypropylene hollow fibres was used in the three-phase extraction of five weak bases from whole blood. The sample work up with the liquid-phase microextraction technique can be impeded by low recovery due to incomplete trapping in the acceptor phase of weakly basic drugs and the complexity of the whole blood matrix. Different parameters related to this problem were experimentally studied. Additionally the stability of the analytes was examined because of low pH in the acceptor phase. The investigation resulted in optimised LPME conditions for the extraction of weak bases from whole blood. The parameters limiting the recovery were evaluated.