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- Kronstrand, Robert, et al.
(författare)
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Analysis of buprenorphine, norbuprenorphine, and their glucuronides in urine by liquid chromatography-mass spectrometry
- 2003
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Ingår i: Journal of Analytical Toxicology. - 0146-4760 .- 1945-2403. ; 27:7, s. 464-470
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Tidskriftsartikel (refereegranskat)abstract
- Buprenorphine is used for the treatment of chronic pain and also in treatment of heroin addiction as an alternative to methadone. As the availability of buprenorphine increases, so does the risk for abuse and the pressure on forensic and clinical laboratories to analyze for it. Buprenorphine and its dealkylated metabolite are excreted in urine, almost exclusively as glucuronides. The aim of the present study was to evaluate electrospray liquid chromatography tandem mass spectrometry (LC-MS-MS) for the rapid screening and quantitation of buprenorphine and its metabolites in urine. Three approaches were evaluated: (1) direct injection of diluted urine for measurement of glucuronides, (2) direct injection of diluted urine after enzymatic hydrolysis for the quantitation of buprenorphine and norbuprenorphine, and (3) quantitation of buprenorphine and norbuprenorphine after enzymatic hydrolysis and solid-phase extraction (SPE). One hundred six samples were subjected to procedure 1 and, when positive, further quantitated using procedure 2. Only samples with low analyte concentrations (< 20 microg/L) were subject to SPE. Concentrations of buprenorphine and norbuprenorphine in patients (N = 16) ranged between 31 and 1080 microg/L and 48-2050 microg/L, respectively. In suspected abusers (N = 33), the ranges were 2.3-796 microg/L and 5.0-2580 microg/L. In four of the authentic samples, both the buprenorphine and norbuprenorphine concentrations were below the 20- micro g/L cutoff. We concluded that LC-MS-MS analysis of the glucuronides provided an adequate screening method, but that the direct method for quantitation sometimes had to be complemented with a concentration by SPE, providing increased sensitivity, thus lowering the cutoff from 20 to 1 microg/L urine.
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| 2. |
- Seldén, Tor, et al.
(författare)
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LC-MS-MS analysis of buprenorphine and norbuprenorphine in whole blood from suspected drug users
- 2011
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Ingår i: Forensic Science International. - : Elsevier. - 0379-0738 .- 1872-6283. ; 209:1-3, s. 113-119
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Tidskriftsartikel (refereegranskat)abstract
- A liquid chromatography tandem mass spectrometry method is described for the analysis of buprenorphine and norbuprenorphine in whole blood. Linearity was achieved between 0.2-5 ng/g for buprenorphine and 0.5-5 ng/g for norbuprenorphine. Stability studies on spiked whole blood and an authentic sample showed no degradation of buprenorphine- and norbuprenorphine-glucuronide to their respective aglycones. Buprenorphine and norbuprenorphine showed some degradation when stored at 4 degrees C for three weeks, but was stable when stored at -20 degrees C for 4 weeks. The method was applied to forensic cases of driving under the influence of drugs (DUID) and petty drug offences (PDO) during 2007-2009. Out of 2459 cases analyzed, 322 were positive for both buprenorphine and norbuprenorphine (13%), 219 for buprenorphine only (9%), and 12 for norbuprenorphine only (0.5%). The mean and median concentrations (N = 322) were 1.7 and 1.0 ng/g, respectively, for buprenorphine and norbuprenorphine. The mean and median norbuprenorphine/buprenorphine ratios were 1.5 and 1.1, respectively. There was no significant difference in concentration ratios for DUID and PDO cases (p andgt; 0.05). We conclude that the described method for analysis of buprenorphine and norbuprenorphine in whole blood could be used to investigate use or misuse of buprenorphine but that many of the cases presented with very low concentrations of buprenorphine. We also conclude that analysis should be performed within two weeks unless samples are stored frozen prior to analysis.
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| 3. |
- Seldén, Tor, et al.
(författare)
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Toxicological and pathological findings in a series of buprenorphine related deaths. Possible risk factors for fatal outcome
- 2012
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Ingår i: Forensic Science International. - : Elsevier. - 0379-0738 .- 1872-6283. ; 220:1-3, s. 284-290
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Tidskriftsartikel (refereegranskat)abstract
- Buprenorphine is considered to have little respiratory side effects at therapeutic doses and the partial agonistic properties should produce a "ceiling effect for respiratory depression at higher doses. Still, there are several reports on buprenorphine related deaths. Most deaths involve drug users and the co-administration of other CNS depressant drugs as well as reduced tolerance have been suggested to be risk factors. The primary aims were to investigate if lack of tolerance and/or co-ingestion of other psychotropic drugs are significant risk factors in buprenorphine fatalities. From July 2005 to September 2009, all autopsy cases where buprenorphine or norbuprenorphine had been detected in femoral blood and where analysis of buprenorphine had been performed in urine were selected. Results from the postmortem examination and toxicology were compiled. Postmortem toxicology was performed using the routine methodology at the laboratory. In total, 97 subjects were included in the study. These were divided into four groups; Intoxication with buprenorphine (N = 41), Possible intoxication with buprenorphine (N = 24), Control cases where buprenorphine was not the cause of death (N = 14), and Unclear (N = 18). The metabolite to parent compound ratios in both blood and urine in the Intoxication group were significantly different from those in the Control and Unclear groups. An extensive poly-drug use was seen in all groups with several additional opioids in the Possible group (54%) and in the Unclear group (78%) and hypnotics or sedatives in more than 75% of the Intoxication, Possible, and Unclear cases. Illicit drugs were present in all groups but not to a great extent with amphetamine and tetrahydrocannabinol as the main findings. Interestingly, 4 cases in the Intoxication group presented with no other significant drugs in blood other than buprenorphine. We conclude that a lethal concentration of buprenorphine in blood cannot be defined. Instead the analysis of blood as well as urine can be an important tool to show that the drug was taken shortly before death and to rule out a continuous use of buprenorphine supporting the notion that abstinence is an important risk factor. The presence of alprazolam in more than 40% of the Intoxications and the presence of hypnotics and sedatives in 75% of the Intoxications suggests that these drugs interact with buprenorphine producing toxic effects that buprenorphine alone would not have produced. Still, in 10% of the Intoxications no other drugs were found indicating that under certain circumstances buprenorphine alone may produce respiratory depression resulting in death.
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