The available alcohol biomarkers vary in sensitivity and specificity with respect to the time period over which they indicate alcohol use and the minimum extent of alcohol use that they can detect. The appropriate marker or combination of markers should be chosen in each case according to the particular question that is to be answered by laboratory analysis.

Phosphatidylethanol (PEth) is a new, highly specific alcohol marker. The aim of this study was to assess its diagnostic value in the liver transplant setting. In 51 pre- and 61 post-transplant patients with underlying alcoholic liver disease PEth, ethanol, methanol, carbohydrate-deficient transferrin (CDT), and ethyl glucuronide in urine (uEtG) and hair (hEtG) were tested and compared with patients' questionnaire reports. Twenty-eight (25%) patients tested positive for at least one alcohol marker. PEth alone revealed alcohol consumption in 18% of patients. With respect to detection of alcohol intake in the preceding week, PEth showed a 100% sensitivity. PEth testing was more sensitive than the determination of ethanol, methanol, CDT or uEtG alone [sensitivity 25% (confidence interval (CI) 95%, 7-52%), 25% (7-52%), 21% (6-45%) and 71% (41-91%), respectively], or ethanol, methanol and uEtG taken in combination with 73% (45-92%). Specificity of all markers was 92% or higher. Additional testing of hEtG revealed alcohol consumption in seven patients, not being positive for any other marker. Phosphatidylethanol was a highly specific and sensitive marker for detection of recent alcohol consumption in pre- and post-transplant patients. The additional determination of hEtG was useful in disclosing alcohol consumption 3-6 months retrospectively.

In any patient with impaired consciousness of unknown cause, the possibility of intoxication with GHB must be considered. Chemical detection of GHB in blood or urine is possible only using specific analytical methods and only within a short time frame (<12 h). Because of the short half-life of GHB, intoxications treated in intensive care units rarely show any complications. However, a number of fatalities have occurred. The potential abuse of GHB as a date rape drug must be borne in mind.

Methadone plays an increasing role in drug-related deaths in Hamburg. To find out whether intravenous application of methadone plays a relevant role in methadone-related deaths, body fluids of all methadone-positive cases (n=130) and three buprenorphine-positive cases where a urine sample was available (n=58+3) were investigated for disaccharides (sucrose and lactose as markers for intravenous methadone abuse). Sixty-four percent of the urine samples of the methadone cases showed positive results for disaccharides (22 times sucrose alone, range 2 to >1,000 mg/L; 6 times lactose and sucrose; and 9 times lactose alone, range 22 to 382 mg/L). The three buprenorphine cases showed positive results for lactose in urine. In blood, it was not possible to detect any disaccharides. Of the 116 fatal methadone intoxications, 49 % were under opiate maintenance treatment (OMT) at the point of death (A-OMT), 30 % were never in OMT (N-OMT) and 21 % were formerly in an OMT, but not at the point of death (F-OMT). Of the deceased in the OMT group, 12 % (n=7) died within the first 2 weeks of treatment, six of them within the first week. Overall, intravenous abuse of methadone plays a relevant role in methadone-related fatal cases of substituted patients and of drug consumers not in therapy. Thus, it is necessary that therapists keep to the statutory regulations and give take-home doses only after at least 6 months of successful therapy and when there is no suspicion of intravenous abuse.

Phosphatidylethanol in blood has gained recognition as a direct alcohol biomarker. Although different cutoffs have been suggested, there is no consensus for differentiating abstinence from alcohol consumption. In this study, 75 participants (72% female) consumed 20 g of ethanol on three consecutive evenings. Blood was sampled on each following day and PEth 16:0/18:1 and 16:0/18:2 were determined. PEth 16:0/18:1 ranged from 8.9–21.5, 8.7–19.3, and 8.8–42.3 ng/ml and PEth 16:0/18:2 from 8.7–31.7, 9.0–39.3, and 9.4–43.0 ng/ml after the respective days of ethanol consumption. PEth 16:0/18:1 yielded a sensitivity of 25%, 45%, and 49% and PEth 16:0/18:2 of 40%, 61%, and 68% for the consumption days, respectively (cutoff 10 ng/ml). PEth 16:0/18:1 reached >20 ng/ml in five samples overall. Sensitivity of PEth 16:0/18:2 > 20 ng/ml was better with 35% after the three drinking days. Overall, PEth 16:0/18:1 was >35 ng/ml in one sample and PEth 16:0/18:2 in three samples. Significantly, more women had PEth 16:0/18:1 > 10 ng/ml after the third day of consuming 20 g of alcohol (p = 0.02) and PEth 16:0/18:2 > 10 ng/ml after the second (p = 0.023) and the third (p = 0.002) consumption, which can be led back to the higher blood alcohol concentration women reach after consuming the same alcohol amount as men. Although the response rates of PEth to alcohol uptake are subject to strong interindividual differences, results suggest that PEth cutoff should be lowered for better detection of consumption of low to medium amounts of alcohol. Furthermore, it is advantageous to analyze both PEth 16:0/18:2 and 16:0/18:1.

Gamma-valerolactone (GVL) is reported to be a substance that can be used as a legal substitute for gamma-hydroxybutyric acid (GHB), which is currently a controlled substance in several countries. Unlike gamma-butyrolactone and 1,4-butanediol, GVL is not metabolized to GHB, which causes the effects after uptake of these two chemicals. In the case of GVL, the lactone ring is split to gamma-hydroxyvaleric acid (GHV or 4-methyl-GHB) by a lactonase. Because of its affinity for the GHB receptor, GHV reveals similar effects to GHB, although it is less potent. Intoxications with GVL, or its use as a date rape drug, are conceivable. Despite these facts, there are no publications in the literature regarding detections of GHV in human samples. This study reports three cases, including five urine samples, in which GHV could be detected in concentrations between 3 and 5.8 mg/L. In one of these cases, a drug-facilitated sexual assault (DFSA) was assumed; four of these samples were from two people suspected of abusing GHB. The results indicate that GVL is used as an alternative to GHB and its precursors and should be taken seriously. GVL or GHV should be included in toxicological analysis, particularly in DFSA cases. More information is needed regarding the pharmacokinetics of GVL/GHV for the meaningful interpretation of positive or negative results.

Our results suggest that it is not possible to quantify the amount of CsA intake by hair analysis. Segmental hair analysis might be useful in the detection of substantial noncompliance and to detect changes in drug-taking behavior.

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