The detection and identification of quaternary nitrogen muscle relaxants in biological fluids and tissues by ion-trap LC-ESI-MS.

Quaternary nitrogen muscle relaxants pancuronium, rocuronium, vecuronium, gallamine, suxamethonium, mivacurium, and atracurium and its metabolites were extracted from whole blood and other biological fluids and tissues by using a solid-phase extraction procedure. The extracts were examined by using high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS). The drugs were separated on a ODS column in a gradient of ammonium acetate buffer (pH 5.0) and acetonitrile. Full-scan mass spectra of the compounds showed molecular ions, and MS-MS spectra showed fragments typical of the particular compounds. LC-ESI-MS allowed an unequivocal differentiation of all muscle relaxants involved. The method was applied in a case of rocuronium and suxamethonium administration in a Caesarian section and in a case of intoxication by pancuronium injection. In both cases, the administered drugs could be detected and identified in the supplied samples.

Driving under the influence of alcohol and/or drugs in the Netherlands 1995-1998 in view of the German and Belgian legislation.

This study presents the test results of blood and urine samples of impaired drivers in the Netherlands between January 1995 and December 1998. In this period, the blood alcohol concentrations of 11,458 samples have been determined and 1665 blood or urine samples have been analysed for drugs. The median alcohol concentration was between 1.7 and 1.8 mg/ml blood. In 80% of the 1665 analysed samples drugs were detected. At least 42% (702/1665) of the impaired drivers were poly-drug users, with cocaine present in the most frequent combinations. In the Netherlands, the procedure to prove driving under the influence is complex. This procedure can be made more efficient and more effective by embedding the analytical test results, needed to prosecute an impaired driver, in the law. In Belgium and Germany, such laws already are in force. If we would apply the qualifications of the new Belgian law on our analytical data, 67% of the impaired drivers included in this comparison could have been prosecuted without discussion in court.

Use of clonidine for chemical submission.

CASE REPORT: An East-European prostitute in Amsterdam robbed several victims, after having sedated them with clonidine solution (available as plastic ampoules of eyedrops) added to her victims' drinks. One victim was hospitalized. His symptoms included bradycardia, hypotension, hypothermia, pallor, cyanosis, and impaired consciousness. Treatment included isoprenaline for 28 hours. The victim was released from hospital the next day. In court, the female offender confessed and was sentenced to prison for 3 1/2 years. She may have administered doses as high as 8 mg clonidine.

Toxicological analysis of whole blood samples by means of Bond-Elut Certify columns and gas chromatography with nitrogen-phosphorus detection.

The application of Bond-Elut Certify solid-phase extraction columns to the systematic toxicological analysis of whole blood was evaluated. The reproducibility of the extraction was tested with thirteen drugs varying in physico-chemical properties. Analysis was performed with capillary gas chromatography with nitrogen-selective detection. The recoveries were reproducible, as long as other limiting factors, e.g., chromatographic behaviour or volatility, do not play a significant role. The effect of limiting chromatographic behaviour was studied in more detail with the more sensitive mass spectrometry with selected-ion monitoring after converting the extracted morphine into its ditrimethylsilyl derivative.

Solid phase extraction of morphine from whole blood by means of Bond Elut Certify columns.

The use of Bond Elut Certify columns for the isolation of morphine from whole blood was evaluated. In order to monitor possible losses and the elution profile of morphine, a small amount of the tritiated analogue was added to the samples. Four sample pretreatment methods, three protein precipitation methods and one sonication/dilution method, were tested. The latter one gave the best results. The blood sample was applied onto the column at pH 3.3 after sonication and dilution with 0.1 M phosphate buffer (pH 3.3). The retention of morphine was affected by the pH of the samples, and the loss of morphine during sample application was minimized at low pH (3.3). The interferences were removed by washing the column with the phosphate buffer, 0.01 M acetic acid (pH 3.3), and methanol, sequentially. Ammoniated methanol, 2 mL at 2%, was selected to elute morphine. As a result, more than 80% of 3H-morphine was recovered for concentrations of morphine ranging from 5 to 4000 ng/mL.

Quantitative liquid chromatography, thermospray/tandem mass spectrometry (LC/TSP/MS/MS) analysis of some thermolabile benzodiazepines in whole-blood.

An LC/TSP/MS/MS selected reaction monitoring (SRM) method in the daughter ion scan mode can be applied successfully for the quantitative determination of thermolabile benzodiazepines in whole-blood following an Extrelut extraction method. Detection limits as low as 100 pg per injection can be reached for all benzodiazepines. The benzodiazepines under investigation proved to be stable, with the exception of ketazolam for which complete degradation to diazepam was observed.

The stability of the alcohol concentration in urine specimens.

The stability of alcohol in urine during storage of up to 12 months was investigated. The decrease in concentration appeared to be limited. No formation of alcohol was observed. It can be concluded that the storage conditions are suitable for forensic purposes.

Determination of delta 9-tetrahydrocannabinol in plasma using solid-phase extraction and high-performance liquid chromatography with electrochemical detection.

A method for the determination of nanogram amounts of delta 9-tetrahydrocannabinol (THC) in plasma and serum is described. THC was quantitatively isolated by solid-phase extraction after addition of an aqueous solution of urea and methanol to the sample. The extracts were analysed by high-performance liquid chromatography with electrochemical detection in the oxidizing mode. The detection limit of THC is ca. 100 pg for a signal-to-noise ratio of 3. With this method, levels of 2 ng/ml of THC in plasma can be measured.

Driving and the combined use of drugs and alcohol in The Netherlands.

The extent and nature of the use of medicinal drugs by drivers who had undergone a blood test on suspicion of driving under the influence of alcohol was ascertained by analysing some 40,000 case records in which the suspect had been questioned about the use of drugs. No chemical analyses were performed. 9.7% of the road users indicated that they used drugs in combination with alcohol, and more than 50% of the drugs used must be considered to have a negative impact on driving performance. The influence of the combined use of benzodiazepines and alcohol on behaviour was also investigated. The finding here was that drivers using these drugs should be warned against the consumption of alcohol.