Lena Kristoffersen

Prevalence of alcohol and drugs among Norwegian motor vehicle drivers: A roadside survey

The objective of the study was to determine the prevalence of alcohol, psychoactive medicinal drugs and illegal drugs among drivers in Norwegian road traffic. Drivers of motor vehicles were selected from April 2005 to April 2006 in the south-eastern part of Norway, surrounding, but not including the capital, Oslo. A stratified two-stage cluster sampling procedure was used. In the first stage, random road sites and time intervals were selected, and in the second stage, drivers were stopped by random at those sites and time intervals. Altogether about 12,000 drivers were asked to provide a sample of oral fluid (saliva) and answer a few questions. Samples of oral fluid were obtained from 88% of the drivers, of whom 30% were females and 70% males. The prevalence of each drug was estimated by a weighted average using weights adjusted for under- or over-sampling compared to traffic statistics. Alcohol or drugs were found in oral fluid samples of 4.5% of the drivers; alcohol in 0.4%, psychoactive medicinal drugs in 3.4%, and illegal drugs in 1.0%. Illegal drugs were found more frequently in samples from younger drivers, while psychoactive medicinal drugs were more frequently found in samples from older drivers. Psychoactive medicinal drugs were more prevalent among females than males, among drivers stopped on working days rather than weekends, and among those who reported annual driving distances less than 16,000 km. The drugs found most frequently were zopiclone (1.4%), benzodiazepines (1.4%), codeine (0.8%), tetrahydrocannabinol (0.6%) and amphetamines (0.3%). Two or more drugs were found in 0.6% of the samples, corresponding to 15% of the drug-positive drivers.

Quantitative determination of fifteen basic pharmaceuticals in ante- and post-mortem whole blood by high pH mobile phase reversed phase ultra high performance liquid chromatography–tandem mass spectrometry ☆

An ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the determination of fifteen basic pharmaceuticals, for analysis of post- and ante-mortem whole blood samples. The following compounds were included: amitriptyline and its metabolite nortriptyline, trimipramine, mianserin, mirtazapine, citalopram, paroxetine, sertraline, and venlafaxine (all antidepressants), levomepromazine and quetiapine (antipsychotics), ketobemidone and tramadol (analgesics), alimemazine (sedative antihistamine), and metoprolol (beta-blocker). The sample pretreatment consisted of liquid-liquid extraction (LLE) using ethylacetate:n-heptane (80:20, v/v). Six deuterated analogues were used as internal standards (IS). The compounds were separated using a reversed phase C18-column (2.1mm×100mm, 1.7μm), a flow rate of 0.5mL/min, and gradient elution with 5mM ammonium formate pH 10.2 and acetonitrile. Quantification was done by MS/MS using multiple reaction monitoring (MRM) in positive mode, using two transitions for the compounds and one transition for the IS. The run time of the method was 8min including equilibration time. The calibration curves had R(2) values above 0.995 for all the compounds. The intermediate precision had a relative standard deviation (RSD, %) ranging between 2.0 and 16%. Recoveries of the compounds were ≥81%. The lower limits of quantifications (LLOQs) for the compounds varied from 5.0nmol/L to 0.10μmol/L (1.3-26ng/mL) and the limits of detections (LODs) from 1.0 to 20nmol/L (0.24-5.3ng/mL). LLOQ corresponds to 0.28-5.5pg injected on column. Matrix effects (ME) were between 91 and 113% when calculated against an IS. A comparison with former confirmation LC-MS methods at the Norwegian Institute of Public Health, Division of Forensic Medicine and Drug Abuse Research (NIPH) was performed during method validation. Good correlation was seen for all compounds except sertraline, where the old LC-MS method was showing 33% higher results. The method has been running on a routine basis for more than a year, and has proven to be very robust and reliable with results for external quality samples, including sertaline, corresponding well to consensus mean or median.

Has the intake of THC by cannabis users changed over the last decade? Evidence of increased exposure by analysis of blood THC concentrations in impaired drivers

The main psychoactive substance, Δ9-tetrahydrocannabinol (THC) can be present in highly variable amounts in different cannabis preparations. An increase in THC content in cannabis products has been suggested, and reported from several countries. However, it has not yet been investigated if products with high potency lead to increased human exposure, and thus to higher risk of adverse effects. In this study, we examined the mean concentrations of THC in whole blood samples from drivers apprehended in Norway in the period between 2000 and 2010 suspected of driving under the influence of drugs. Cases with only THC (n=1747) have been compared to cases with only ethanol (n=38796) or amphetamines (n=2493). The increase in mean THC concentration measured from 2000 to 2010 was from 4.0 ± 0.3 to 6.6 ± 0.4 ng/ml (58%), compared to 3% for ethanol and 16% for the amphetamines. This increase in THC concentrations was to some extent paralleled by an increase in the percentage of drivers which were judged as lightly impaired by a physician. Monitoring concentrations of drugs of abuse in blood from apprehended drivers indicated an increasing exposure to THC in Norway. If similar trends are observed globally, it should be further explored if this type of information could be used to elucidate the drug consumption patterns in a population and accordingly the consequences with regard to adverse effects of cannabis from a public health perspective.

Quantitative determination of zopiclone and zolpidem in whole blood by liquid–liquid extraction and UHPLC-MS/MS

An ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the determination of zopiclone and zolpidem in whole blood, for use in cases with suspected driving under influence of drugs (DUID) and autopsy cases. Sample preparation was performed with liquid-liquid extraction (LLE) using ethyl acetate/n-heptane (80:20, v/v) and 0.1mL whole blood. Deuterated analogues were used as internal standards (IS) for both compounds. The compounds were separated using a reversed phase C18-column (2.1mm×100mm, 1.7μm), with a flow rate of 0.5mL/min, 1μL injected and gradient elution with 5mM ammonium formate pH 10.2 and acetonitrile. Quantification was done by MS/MS using multiple reaction monitoring (MRM) in positive mode. The run time of the method was 4.5min including equilibration time. The calibration curves of extracted whole blood standards were fitted by linear-order calibration curves weighted 1/x, with R(2) values above 0.999 for both compounds. Intermediate precision and accuracies (bias) were 2.4-12.9% RSD and from -5.9 to 6.8%, respectively. Recoveries of the compounds were ≥70%. The lower limit of quantification (LLOQ) for zopiclone was 0.50nmol/L (0.19ng/mL) or 0.05pg injected on column, and 3.5nmol/mL (1.10ng/mL) for zolpidem, or 0.27pg injected on column. The limit of detection (LOD) was 0.2nmol/L (0.08ng/mL) for zopiclone and 0.3nmol/L (0.09ng/mL) for zolpidem. Matrix effects (ME) were between 108 and 115% when calculated against IS. A comparison with former confirmation LC-MS method at the Norwegian Institute of Public Health, Division of Forensic Medicine (NIPH) was performed during method validation. Good correlation was seen for both compounds. The method has been running on a routine basis for two years, and has proven to be very robust and reliable with satisfactory long term precision and bias and with results for external quality samples corresponding well to consensus mean or median. Zopiclone and zolpidem concentrations in post mortem and ante mortem cases were reported. The method also meets the requirements of the legislative limits for driving under the influence of non-alcohol drugs introduced in the Norwegian Road Traffic Act Law from 2012.

Ethanol elimination rates at low concentrations based on two consecutive blood samples

INTRODUCTION For ethanol, the elimination curve change from apparent zero to apparent first order kinetics at low blood alcohol concentrations (BACs). This is less studied than elimination at higher BACs, and knowledge about this low BAC elimination is especially missing in drunk drivers representing a population with a high frequency of heavy drinkers with increased rate of ethanol metabolism. The aim of this study was to investigate the point at which elimination rates turns from zero to first order kinetics and the exact elimination rates at the very low BAC intervals in drunk drivers. METHODS Two consecutively collected samples from suspected drunk drivers were used. All samples were analyzed by two headspace gas chromatography flame ionization detector methods (limit of quantification=0.04g/kg). The elimination rates at BACs below 0.25g/kg (study group, n=175) was studied in detail, and compared to the elimination rates in a moderate BAC reference group (n=789) as well as a high BAC reference group (n=4435). RESULTS There were no differences in age, gender and drivings occurring during night-time between the study group and the reference groups. The mean elimination rates were stable at 0.18-0.19g/kg/h from a BAC of 4.0g/kg and until BAC in the first blood sample fell below 0.19g/kg. At BACs below 0.19g/kg, the mean elimination rate gradually declined from 0.163g/kg/h to the lowest elimination rate of 0.083g/kg/h. There was no relation between the concentration of ethanol and elimination rate at BACs above 0.19g/kg (Pearsons r=0.035, p=0.3), but there was a strong relation between concentration of ethanol and elimination rate at BACs below 0.19g/kg (Pearsons r=0.56, p<0.001). CONCLUSION In conclusion, the present study showed that in a population of drunk drivers, the shift from zero order to first order kinetics occurs when BAC falls below 0.19g/kg. Below this points, the present study indicate that drunk drivers show elimination rates comparable to the normal population. These results could assist in back-calculations in cases of drunk driving involving low BACs.

Bestemmelse av legemidler og rusmidler i hår

2. What drugs can VIFM test for with hair? VIFM can test for at least 60 drugs in hair. This includes common illicit drugs such as methylamphetamine, heroin, cocaine and cannabis. VIFM can also test for a number of prescription drugs including an extensive range of stimulants, benzodiazepines (sedatives), opioids, barbiturates, antidepressants, anaesthetics, antipsychotics and new synthetic drugs.