Enantiomer-specific analysis of amphetamine in urine, oral fluid and blood.

Illegal amphetamine is usually composed of a racemic mixture of the two enantiomers (S)- and (R)-amphetamine. However, when amphetamine is used in medical treatment, the more potent (S)-amphetamine enantiomer is used. Enantiomer-specific analysis of (S)- and (R)-amphetamine is therefore used to separate legal medical use from illegal recreational use. The aim of the present study was to describe our experience with enantiomer-specific analysis of amphetamine in urine and oral fluid, as well as blood, and examine whether the distribution of the two enantiomers seems to be the same in different matrices. We investigated 1,722 urine samples and 1,977 oral fluid samples from prison inmates, and 652 blood samples from suspected drugged drivers, where prescription of amphetamine was reported. Analyses were performed using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS-MS). The enantiomer separation was achieved by using a chiral column, and results from the method validation are reported. Samples containing <60% (S)-amphetamine were interpreted as representing illegal use of amphetamine. The distribution of the two enantiomers was compared between different matrices. In urine and oral fluid, the mean amount of (S)-amphetamine was 45.2 and 43.7%, respectively, while in blood, the mean amount of (S)-amphetamine was 45.8%. There was no statistically significant difference in the amount of (S)-amphetamine between urine and oral fluid samples and between urine and blood samples, but the difference was significant in blood compared to oral fluid samples (P < 0.001). Comparison of urine and oral fluid between similar populations indicated that enantiomers of amphetamine can be interpreted in the same way, although marginally higher amounts of (R)-amphetamine may occur in oral fluid. Oral fluid, having several advantages, especially during collection, could be a preferred matrix in testing for illegal amphetamine intake in users of medical amphetamine.

Oral Fluid to Blood Concentration Ratios of Different Psychoactive Drugs in Samples from Suspected Drugged Drivers.

BACKGROUND: The ratio between the concentrations of drugs in the oral fluid and blood (OF/B ratio) reflects the transfer of drugs from blood to oral fluid, which is influenced by several factors such as oral fluid contamination. OF/B drug concentration ratios for psychoactive drugs, including interindividual variation, were investigated in this study. For a portion of the material, oral fluid concentrations in both sides of the mouth were compared. METHODS: Samples of whole blood and oral fluid collected using the Intercept device were obtained from 489 suspected drugged drivers. Concentrations of amphetamine, methamphetamine, THC, diazepam, N-desmethyldiazepam, clonazepam, alprazolam, oxazepam, nitrazepam, morphine, buprenorphine, and methadone were determined in blood and oral fluid samples using liquid chromatography-tandem mass spectrometry. RESULTS: Median OF/B ratios were 18.6 for amphetamine, 13.8 for methamphetamine, 3.8 for morphine, 24.8 for buprenorphine, 3.7 for methadone, 0.026 for diazepam, 0.031 for N-desmethyldiazepam, 0.28 for alprazolam, 0.16 for clonazepam, 0.12 for oxazepam, 0.099 for nitrazepam, and 4.3 for THC. Large interindividual variations in OF/B ratios were observed. The median difference in concentrations in oral fluid from both sides of the mouth was less than 20% for all drugs, except THC and buprenorphine, which had median differences of 32%-34%. CONCLUSIONS: High OF/B ratios were found for amphetamines and opioids, reflecting a high degree of drug transfer from blood to oral fluid and a longer detection window in oral fluid than in blood. For benzodiazepines, low OF/B ratios were found. Results of the concentration measurements in oral fluid from both sides of the mouth could indicate that some remnants of THC and buprenorphine were present in the oral cavity. The large variations among individuals and between the 2 sides of the mouth suggest that drug concentrations in oral fluid do not accurately reflect drug concentrations in the blood.

Detection of Drugs in Simultaneously Collected Samples of Oral Fluid and Blood.

Simultaneously collected samples of oral fluid and blood in a naturalistic setting could provide a qualitative impression of the relative detection times of drugs in oral fluid compared to blood. The aim of this study was to compare detections of different drugs in oral fluid and blood from a large material of paired samples. The study included results from 930 paired oral fluid and blood samples collected from drivers suspected for driving under the influence of drugs. Oral fluid was collected using the Intercept device. Blood samples were screened using an ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS-MS) method and positive results were confirmed and quantified with a different analytical method. Oral fluid samples were analyzed using UHPLC-MS-MS. The drugs included in the study were: amphetamine, methamphetamine, tetrahydrocannabinol (THC), diazepam, N-desmethyldiazepam, clonazepam, alprazolam, nitrazepam, oxazepam, morphine, 6-monoacetylmorphine (6-MAM), methadone and buprenorphine. The drugs detected more frequently in oral fluid compared to blood were amphetamine (497 positive in oral fluid/408 positive in blood), methamphetamine (332/232), oxazepam (106/36), morphine (65/31) and 6-MAM (19/0). The drugs detected less frequently in oral fluid compared to blood were THC (224 positive in oral fluid/407 positive in blood), diazepam (137/160), N-desmethyldiazepam (183/188), clonazepam (148/307), alprazolam (47/68), nitrazepam (16/29) and buprenorphine (31/59). For methadone, the number of detections was the same in oral fluid and in blood (23/23). The results indicate that for amphetamine, methamphetamine, morphine and 6-MAM, relative detection time is longer in oral fluid than in blood, while for benzodiazepines, the results indicate that relative detection time is shorter in oral fluid than in blood. For oxazepam and buprenorphine, the results were dependent on the cut-off limits used. Regarding THC, the detection time in oral fluid depends on the sampling method. The relative detection time was shorter than in blood when using the Intercept device.

Influence of alcohol and other substances of abuse at the time of injury among patients in a Norwegian emergency department.

BACKGROUND: The presence of alcohol or other substances of abuse in blood or urine from injured patients is often used as a proxy for substance influence at the time of injury. The aim of this study was to obtain an estimate of substance influence at the time of injury based on blood concentrations of alcohol and other substances of abuse, and to explore the relationship between the substance prevalence at the time of admittance to the hospital and the actual influence at the time of the injury. METHODS: The study included all adult patients admitted to the emergency department of a university hospital during 1 year (n = 996). Quantification in blood was done by an enzymatic method for alcohol, and by liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry for 28 other substances of abuse. Concentrations of alcohol and other substances in blood at the time of injury were calculated. The degree of influence was assessed on the basis of the calculated blood concentrations, with a threshold of influence set at a blood alcohol concentration (BAC) of 0.05 %, or a substance concentration leading to an influence similar to that of a BAC of 0.05 %. RESULTS: A total of 324 patients (32.5 %) were determined to be under the influence at the time of injury. In comparison, 394 patients (39.6 %) had one or more substances above the cut-off limit in blood at the time of admittance to the hospital. Alcohol was the most prevalent substance causing influence at 25.9 %. Among patients with violence-related injuries, almost 75 % were under the influence of alcohol and/or substances. Patients under the influence were younger, and men were more often under the influence than women. More patients were under the influence at nighttime and during weekends than at daytime and on weekdays. CONCLUSIONS: About one third of the injured patients were determined to be under the influence at the time of injury, with alcohol being the most prevalent substance causing influence. Approximately 98 % of the patients with alcohol detected in blood at the time of admittance to the hospital were under the influence of alcohol at the time of injury.

Controlling for high-density lipoprotein cholesterol does not affect the magnitude of the relationship between alcohol and coronary heart disease.

BACKGROUND: This study tested the hypothesis that moderate alcohol intake exerts its cardioprotective effect mainly through an increase in the serum level of high-density lipoprotein cholesterol. METHODS AND RESULTS: In the Cohort of Norway (CONOR) study, 149 729 adult participants, recruited from 1994 to 2003, were followed by linkage to the Cause of Death Registry until 2006. At recruitment, questionnaire data on alcohol intake were collected, and the concentration of high-density lipoprotein cholesterol in serum was measured. Using Cox regression, we found that the adjusted hazard ratio for men for dying from coronary heart disease was 0.52 (95% confidence interval, 0.39-0.69) when consuming alcohol more than once a week compared with never or rarely. The ratio changed only slightly, to 0.55 (0.41-0.73), after the regression model included the serum level of high-density cholesterol. For women, the corresponding hazard ratios were 0.62 (0.32-1.23) and 0.68 (0.34-1.34), respectively. CONCLUSIONS: Alcohol intake is related to a reduced risk of death from coronary heart disease in the follow-up of a large, population-based Norwegian cohort study with extensive control for confounding factors. Our findings suggest that the serum level of high-density cholesterol is not an important intermediate variable in the possible causal pathway between moderate alcohol intake and coronary heart disease.

[Interactions with methadone and buprenorphine]. / Interaksjoner med metadon og buprenorfin.

In Norway, about 5000 patients receive opioid maintenance treatment; 60 % receive methadone and 40 % buprenorphine. An increasing number of regular general practitioners and hospital doctors are in contact with this group of patients. This article presents a short overview of drug interactions with methadone and buprenorphine, as an aid to medical doctors in contact with these patients.