| 1. |
- Bendroth, Peter, et al.
(författare)
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Comparison of ethyl glucuronide in hair with phosphatidylethanol in whole blood as post-mortem markers of alcohol abuse
- 2008
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Ingår i: Forensic Science International. - : Elsevier BV. - 0379-0738 .- 1872-6283. ; 176:1, s. 76-81
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Tidskriftsartikel (refereegranskat)abstract
- Ethyl glucuronide (EtG) is a direct metabolite of ethanol and has been used as a marker of alcohol abuse in both urine and hair. This study investigated the value of EtG testing in post-mortem hair for diagnostic improvement of alcohol abuse in forensic medicine. Material from 70 consecutive medico-legal autopsies was collected in accordance with the recommendations on ethics by the Swedish National Board of Forensic Medicine. A method for determination of EtG in hair samples was developed using ultra performance liquid chromatography/electrospray tandem mass spectrometry (UPLC/ESI-MS/MS; LOQ, 2.5 pg/mg). The result of the EtG analysis was compared with the findings of phosphatidylethanol (PEth) in femoral whole blood, as measured by high performance liquid chromatography with an evaporative light-scattering detector (HPLC–ELSD; LOQ, 0.22 μmol/l). Evaluation of liver histology and anamnestic evidence of alcohol abuse of the deceased were taken in consideration for the interpretation. Measurable levels of EtG were present in 49 of the 70 autopsy cases whereas PEth was present in 36. Thirty-nine cases had EtG levels above the cutoff limit (≥30 pg/mg) compared with 29 for PEth (≥0.7 μmol/l). Fifteen cases had EtG as exclusive indicator for alcohol abuse compared with four cases for PEth. These findings suggest that measurements of EtG in hair may provide improved diagnostic information on alcohol abuse, due to a long retrospective time-window for detection and stability of EtG in hair in the decaying cadaver. However, an EtG level below the cutoff does not completely exclude previous alcohol abuse.
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| 2. |
- Bruhn, Jan G., et al.
(författare)
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Ecstasy analogues found in cacti
- 2008
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Ingår i: Journal of Psychoactive Drugs. - : Informa UK Limited. - 0279-1072 .- 2159-9777. ; 40:2, s. 219-222
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Tidskriftsartikel (refereegranskat)abstract
- Human interest in psychoactive phenethylamines is known from the use of mescaline-containing cacti and designer drugs such as Ecstasy. From the alkaloid composition of cacti we hypothesized that substances resembling Ecstasy might occur naturally. In this article we show that lophophine, homopiperonylamine and lobivine are new minor constituents of two cactus species, Lophophora williamsii (peyote) and Trichocereus pachanoi (San Pedro). This is the first report of putatively psychoactive phenethylamines besides mescaline in these cacti. A search for further biosynthetic analogues may provide new insights into the structure-activity relationships of mescaline. An intriguing question is whether the new natural compounds can be called "designer drugs."
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| 3. |
- Stephanson, Nikolai, et al.
(författare)
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Accurate identification and quantification of 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid in urine drug testing: Evaluation of a direct high efficiency liquid chromatographic-mass spectrometric method
- 2008
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Ingår i: Journal of chromatography. B. - : Elsevier Science B.V., Amsterdam.. - 1570-0232 .- 1873-376X. ; 871:1, s. 101-108
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Tidskriftsartikel (refereegranskat)abstract
- A direct liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for measurement of urinary Delta(9)-tetrahydrocannabinol carboxylic acid (THCA) was developed. The method involved dilution of the urine sample with water containing H-2(9)-deuterated analogue as internal standard, hydrolysis with ammonia, reversed phase chromatography using a Waters ultra-performance liquid chromatography (UPLC (TM)) equipment with gradient elution, negative electrospray ionization, and monitoring of two product ions in selected reaction monitoring mode. The measuring range was 2-1000 ng/mL for THCA, and the intra- and inter-assay imprecision, expressed as the coefficient of variation, was below 5%. Influence from urine matrix on ionization efficiency was noted in infusion experiments, but was compensated for by the internal standard. Comparison with established gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry methods in authentic patient samples demonstrated accuracy in both qualitative and quantitative results. A small difference in mean ratios (similar to 15%) may be explained by the use of different hydrolysis procedures between methods. In conclusion, the high efficiency LC-MS/MS method was capable of accurately identify and quantify THCA in urine with a capacity of 14 samples per hour.
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| 4. |
- Stephanson, Niclas Nikolai
(författare)
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Liquid chromatography : mass spectrometry study of two biochemical alcohol markers
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The interest in biochemical alcohol markers for detecting acute and chronic alcohol consumption has expanded greatly during recent years. The development and application of laboratory tests identifying early problematic drinking and monitoring abstinence have the potential of reducing the healthcare costs and suffering associated with alcohol misuse. Laboratory tests which are sensitive enough to detect single alcohol intake include ethanol, ethyl glucuronide (EtG) and 5-hydroxytryptophol glucuronide (GTOL). The overall aim of the present work was development of sensitive and specific liquid chromatography-mass spectrometry (LC-MS) methods for direct quantification of EtG and GTOL in urine, and to apply these for clinical studies. EtG is a minor direct metabolite of ethanol, and is present for some time after ethanol is eliminated. A simple analytical procedure was developed based on direct injection of diluted urine into the LC-MS system. EtG was found to be stable in urine with no breakdown or artificial formation on storage in room temperature. Presence of ethanol in urine did not result in any artificial formation. EtG was not detectable in urine samples collected after abstinence from alcohol. EtG remains in the urine for many hours after ethanol itself has been eliminated. Thus, testing urine for the presence of EtG provides a mean for determination of recent alcohol consumption. Expressing urinary EtG as a ratio to creatinine should be recommended in routine clinical use to compensate for urine dilution. The method fulfils the need for a simple and reliable assay to be used as a routine test of recent alcohol intake. GTOL is the major excretion form of 5-hydroxytryptophol (5-HTOL), a minor serotonin (5-HT) metabolite. Because the concentration of 5-HTOL is markedly increased following consumption of alcohol, measurement of 5-HTOL is used as a sensitive biomarker for detection of recent alcohol intake. An LC-MS procedure, including solid-phase extraction for direct quantification of GTOL was developed. The method was highly correlated with an established gas chromatography-MS method for urinary 5-HTOL (r2 = 0.99, n = 70; mean 5-HTOL/GTOL = 1.10). This was the first direct assay for quantification of GTOL in urine, suitable for routine application. In clinical use, GTOL is expressed as a ratio to the main 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA), in order to compensate for variations in urine dilution and 5-HT turnover. A fully validated and robust LC-MS/MS method for measurement of urinary GTOL and 5-HIAA, based on direct injection was developed. The method was capable of measuring endogenous GTOL and 5-HIAA levels in urine that agreed with literature data. The method was applied and compared with a new developed enzyme-linked immunosorbent assay (ELISA) for GTOL in clinical material. Determination of GTOL by ELISA showed 82% sensitivity in detecting positive samples, compared to the LC-MS/MS method. When 10 alcoholic patients were followed during detoxification, the GTOL/5-HIAA ratio gave a median detection time of 39 hours, while EtG was detectable for a median of 65 hours. The lower sensitivity of the urinary GTOL/5-HIAA ratio compared with EtG for recent drinking may be clinically useful, in cases where the EtG test provides an unwanted high sensitivity for intake of only small amounts of alcohol or unintentional ethanol exposure. The present work demonstrated the potential of developing robust and selective methods for quantification of analytes in urine using electrospray ionization LC-MS and LC-MS/MS with minimal sample preparation.
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