gamma-Hydroxybutyric acid (GHB) has been widely associated with drug-facilitated sexual assault (DFSA). However, its excretion profile in man has not been well characterized. To assess the detectability of GHB for forensic cases and to correlate urinary levels with dose, we have examined the excretion profiles of 1- and 2-g doses of GHB (sodium salt) in a healthy male volunteer. The urinary levels were measured by a novel, simple and highly reproducible method. The drug was found to be excreted in small amounts in the free form (0.86 and 1.16% for 1- and 2-g doses, respectively) rapidly in urine (< or = 10 h). The urinary levels were found to be in the low mg L(-1) range (up to 29.1 mg L(-1)). The work presented demonstrates that it is of the utmost importance to collect the samples as soon as possible following the alleged assault.
The measurement of the urinary free cortisol-cortisone ratio has been reported to be a sensitive indicator of renal 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD 2) activity. This converts biologically active cortisol to inactive cortisone. A decrease in its activity (e.g. through disease or inhibition caused by a therapeutic agent or a foodstuff) may increase cortisol levels and susceptibility towards hypertension. The method presented here uses a simple isocratic tandem column HPLC system. The method has been validated and found to be robust and reproducible. The lower limit of quantification (LLOQ) was found to be 10 ng/mL for both cortisol and cortisone. Samples of urine (n = 99) from patients, most of whom were on complex combinations of drugs, were analyzed and 92% of samples were found to give successful results with this method (cortisol and cortisone above LLOQ). The ratio ranged from 0.07 to 5.61. No interferences were noted from the drugs that the patients were taking. It was also found that a morning spot urine sample gave comparable results to 24 h collection samples, thus making sample collection much easier.
The objective of this study was to develop an immunoassay that would be capable of detecting flunitrazepam and/or cross-reacting metabolites in urine and comparing the results with those obtained by gas chromatography-mass spectrometry. Doses of Rohypnol varying between 0.5 and 4 mg were given to volunteers, and urine was collected for up to two weeks postingestion. These samples were analyzed by an ELISA that was developed using an antibody raised to flunitrazepam and a drug-enzyme conjugate prepared by attaching 7-aminoflunitrazepam to horseradish peroxidase. Significant levels of flunitrazepam and/or cross-reacting metabolites were detected in urine for up to one week after ingestion. The immunoassay is selective with only diazepam cross-reacting at a level of 1000 microg/L.
Background Age-related changes in arterial stiffness are ascribed to collagen and elastin content in the aorta (Ao) which is modulated by the matrix metalloprotienases (MMPs). However, no study has directly compared arterial stiffness and arterial structure in man. Methods Aortic and internal mammary artery (IMA) tissue were obtained from 10 patients (62±1 years, 2 female) undergoing coronary artery bypass grafting (CABG). Aortic pulse wave velocity (PWV) was measured prior to CABG. Collagen content was assessed in tissue sections using Sirius Red staining and elastin by ACCUSTAIN. Elastin fragmentation in the Ao media was graded; increasing in severity from 1 to 4. MMP-2 and MMP-9 activity was quantified in the Ao using gelatine zymography. Results are expressed as mean±SEM, p<0.05 considered significant. Results The collagen concentration was 50% (intima), 42% (media)and 76% (adventitia) in the Ao but was lower in the IMA. PWV was significantly associated with Ao medial (r=0.79, p=0.03) but not intimal or adventitial collagen concentrations. Aortic intimal thickness was related significantly with age (r=0.70, p<0.05) but not PWV. There was no relationship between age and Ao collagen concentration. There was a significant association (p<0.001) between increasing elastin fragmentation in the aortic media and PWV but not age. There was no relationship between collagen concentration in the IMA and either PWV or age. Neither latent nor active MMP-2 activity was related with PWV or age. Latent MMP-9 expression was significantly associated with PWV (r=0.66, p<0.05) but not age. Conclusions Our proof-of-concept study is the first one to show that elastin fragmentation in the aorta may underlie arterial stiffening in man. In contrast, the internal mammary artery does not age, unlike the aorta, which makes it the reassuring choice for coronary artery bypass grafting. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Health Research Board, Ireland
4-Methylthioamphetamine (4-MTA) is a new drug of abuse, and owing to a number of deaths in the EU over a 2-year period, it has become a major cause for concern. Little is known about the metabolism, half-life or excretion pro®le of 4-MTA, in man. We used a canine model to study the excretion pro®le of 4-MTA.Urine samples were screened for 4-MTA with EMIT amphetamine immunoassay, followed by con®rmatory analysis using GC-MS. 4-MTA was detectable using EMITamphetamine immunoassay down to 1 mg mL À1 in drug-free urine samples to which 4-MTA was added. 4-MTA was detectable by EMIT up to 23 h after administration. Base extracted urine samples were subjected to¯ash derivatization using N-methylbis(tri¯uoroacetamide) and the resulting tri¯uoroacetylated compound yielded a well fragmented mass spectrum under the GC-MS conditions used. Quanti®cation of 4-MTA in the urine samples revealed 15, 11 and 20 mg mL À1 at 5Á5, 13Á5 and 23 h, respectively. 4-MTA is detectable by immunoassay at 1 mg mL À1 and can be detected in dogs up to 23 h after administration. EMIT positive screens can be checked using GC-MS incorporating derivatization to con®rm the presence of 4-MTA.
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