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Kronstrand, Robert
Publications (10 of 56) Show all publications
Olsson, M. O., Öjehagen, A., Brådvik, L., Kronstrand, R. & Håkansson, A. (2017). High Rates of Tramadol Use among Treatment-Seeking Adolescents in Malmö, Sweden: A Study of Hair Analysis of Nonmedical Prescription Opioid Use. Journal of addiction, 2017, Article ID 6716929.
Open this publication in new window or tab >>High Rates of Tramadol Use among Treatment-Seeking Adolescents in Malmö, Sweden: A Study of Hair Analysis of Nonmedical Prescription Opioid Use
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2017 (English)In: Journal of addiction, ISSN 2090-7850, Vol. 2017, article id 6716929Article in journal (Refereed) Published
Abstract [en]

Nonmedical prescription opioid use (NMPOU) is a growing problem and tramadol has been suggested as an emerging problem in young treatment-seeking individuals. The aim of the present study was to investigate, through hair analysis, NMPOU in this group and, specifically, tramadol use.

Place, publisher, year, edition, pages
Hindawi Publishing Corporation, 2017
National Category
Substance Abuse Forensic Science
Identifiers
urn:nbn:se:liu:diva-146361 (URN)10.1155/2017/6716929 (DOI)29435382 (PubMedID)
Available from: 2018-04-07 Created: 2018-04-07 Last updated: 2018-04-25
Swortwood, M. J., Ellefsen, K. N., Wohlfarth, A., Diao, X., Concheiro-Guisan, M., Kronstrand, R. & Huestis, M. A. (2016). First metabolic profile of PV8, a novel synthetic cathinone, in human hepatocytes and urine by high-resolution mass spectrometry. Analusis, 408(18), 4845-4856
Open this publication in new window or tab >>First metabolic profile of PV8, a novel synthetic cathinone, in human hepatocytes and urine by high-resolution mass spectrometry
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2016 (English)In: Analusis, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 408, no 18, p. 4845-4856Article in journal (Refereed) Published
Abstract [en]

Novel psychoactive substances (NPS) are ever changing on the drug market, making it difficult for toxicology laboratory methods to stay current with so many new drugs. Recently, PV8, a synthetic pyrrolidinophenone, was detected in seized products in Japan (2013), The Netherlands (2014), and Germany (2014). There are no controlled PV8 administration studies, and no pharmacodynamic and pharmacokinetic data. The objective was to determine PV8s metabolic stability in human liver microsome (HLM) incubation and its metabolism following human hepatocyte incubation and high-resolution mass spectrometry (HRMS) with a Thermo Scientific Q-Exactive. Data were acquired with a full-scan data-dependent mass spectrometry method. Scans were thoroughly data mined with different data processing algorithms and analyzed in WebMetaBase. PV8 exhibited a relatively short 28.8 min half-life, with an intrinsic 24.2 mu L/min/mg microsomal clearance. This compound is predicted to be an intermediate clearance drug with an estimated human 22.7 mL/min/kg hepatic clearance. Metabolic pathways identified in vitro included: hydroxylation, ketone reduction, carboxylation, N-dealkylation, iminium formation, dehydrogenation, N-oxidation, and carbonylation. The top three in vitro metabolic pathways were di-hydroxylation amp;gt; ketone reduction amp;gt; gamma-lactam formation. Authentic urine specimen analyses revealed the top three metabolic pathways were aliphatic hydroxylation amp;gt; ketone reduction + aliphatic hydroxylation amp;gt; aliphatic carboxylation, although the most prominent peak was parent PV8. These data provide useful urinary metabolite targets (aliphatic hydroxylation, aliphatic hydroxylation + ketone reduction, aliphatic carboxylation, and di-hydroxylation) for forensic and clinical testing, and focus reference standard companies synthetic efforts to provide commercially available standards needed for PV8 biological specimen testing.

Place, publisher, year, edition, pages
SPRINGER HEIDELBERG, 2016
Keyword
PV8; Novel psychoactive substances; Metabolic profiling; HRMS; Hepatocytes; Synthetic cathinones
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:liu:diva-130414 (URN)10.1007/s00216-016-9599-4 (DOI)000378999500004 ()27185540 (PubMedID)
Note

Funding Agencies|National Institute on Drug Abuse, National Institutes of Health

Available from: 2016-08-15 Created: 2016-08-05 Last updated: 2018-03-22
Diao, X., Scheidweiler, K. B., Wohlfarth, A., Pang, S., Kronstrand, R. & Huestis, M. A. (2016). In Vitro and In Vivo Human Metabolism of Synthetic Cannabinoids FDU-PB-22 and FUB-PB-22. AAPS Journal, 18(2), 455-464
Open this publication in new window or tab >>In Vitro and In Vivo Human Metabolism of Synthetic Cannabinoids FDU-PB-22 and FUB-PB-22
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2016 (English)In: AAPS Journal, ISSN 1550-7416, E-ISSN 1550-7416, Vol. 18, no 2, p. 455-464Article in journal (Refereed) Published
Abstract [en]

In 2014, FDU-PB-22 and FUB-PB-22, two novel synthetic cannabinoids, were detected in herbal blends in Japan, Russia, and Germany and were quickly added to their scheduled drugs list. Unfortunately, no human metabolism data are currently available, making it challenging to confirm their intake. The present study aims to identify appropriate analytical markers by investigating FDU-PB-22 and FUB-PB-22 metabolism in human hepatocytes and confirm the results in authentic urine specimens. For metabolic stability, 1 mu M FDU-PB-22 and FUB-PB-22 was incubated with human liver microsomes for up to 1 h; for metabolite profiling, 10 mu M was incubated with human hepatocytes for 3 h. Two authentic urine specimens from FDU-PB-22 and FUB-PB-22 positive cases were analyzed after beta-glucuronidase hydrolysis. Metabolite identification in hepatocyte samples and urine specimens was accomplished by high-resolution mass spectrometry using information-dependent acquisition. Both FDU-PB-22 and FUB-PB-22 were rapidly metabolized in HLM with half-lives of 12.4 and 11.5 min, respectively. In human hepatocyte samples, we identified seven metabolites for both compounds, generated by ester hydrolysis and further hydroxylation and/or glucuronidation. After ester hydrolysis, FDU-PB-22 and FUB-PB-22 yielded the samemetabolite M7, fluorobenzylindole-3-carboxylic acid (FBI-COOH). M7 and M6 (hydroxylated FBI-COOH) were the major metabolites. In authentic urine specimens after beta-glucuronidase hydrolysis, M6 and M7 also were the predominant metabolites. Based on our study, we recommend M6 (hydroxylated FBI-COOH) and M7 (FBI-COOH) as suitable urinary markers for documenting FDU-PB-22 and/or FUB-PB-22 intake.

Place, publisher, year, edition, pages
SPRINGER, 2016
Keyword
FDU-PB-22; FUB-PB-22; hepatocyte metabolism; high-resolution mass spectrometry; synthetic cannabinoid
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:liu:diva-127050 (URN)10.1208/s12248-016-9867-4 (DOI)000371977400019 ()26810398 (PubMedID)
Note

Funding Agencies|Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health

Available from: 2016-04-13 Created: 2016-04-13 Last updated: 2018-03-26
Swortwood, M. J., Carlier, J., Ellefsen, K. N., Wohlfarth, A., Diao, X., Concheiro-Guisan, M., . . . Huestis, M. A. (2016). In vitro, in vivo and in silico metabolic profiling of -pyrrolidinopentiothiophenone, a novel thiophene stimulant. Bioanalysis, 8(1), 65-82
Open this publication in new window or tab >>In vitro, in vivo and in silico metabolic profiling of -pyrrolidinopentiothiophenone, a novel thiophene stimulant
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2016 (English)In: Bioanalysis, ISSN 1757-6180, E-ISSN 1757-6199, Vol. 8, no 1, p. 65-82Article in journal (Refereed) Published
Abstract [en]

Background: Little or no pharmacological or toxicological data are available for novel psychoactive substances when they first emerge, making their identification and interpretation in biological matrices challenging. Materials & methods: A new synthetic cathinone, alpha-pyrrolidinopentiothiophenone (alpha-PVT), was incubated with hepatocytes and samples were analyzed using liquid chromatography coupled to a Q Exactive(TM) Orbitrap mass spectrometer. Authentic urine specimens from suspected -PVT cases were also analyzed. Scans were data mined with Compound Discoverer for identification and structural elucidation of metabolites. Results/conclusion: Seven alpha-PVT metabolites were identified in hepatocyte incubations, and in the authentic urine samples, also with an additional monohydroxylated product and a glucuronide of low intensity. alpha-PVT dihydroxypyrrolidinyl, alpha-PVT 2-ketopyrrolidinyl, alpha-PVT hydroxythiophenyl and alpha-PVT thiophenol had the most intense in vivo signals.

Place, publisher, year, edition, pages
FUTURE SCI LTD, 2016
Keyword
alpha-PVT; hepatocytes; high-resolution MS; metabolism; novel psychoactive substances; synthetic cathinone
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-124095 (URN)10.4155/bio.15.237 (DOI)000367012500008 ()26648097 (PubMedID)
Note

Funding Agencies|Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health

Available from: 2016-01-25 Created: 2016-01-19 Last updated: 2017-11-30
Haage, P., Kronstrand, R., Carlsson, B. & Josefsson, M. (2016). Quantitation of the enantiomers of tramadol and its three main metabolites in human whole blood using LC-MS/MS.. Journal of Pharmaceutical and Biomedical Analysis, 119, 1-9
Open this publication in new window or tab >>Quantitation of the enantiomers of tramadol and its three main metabolites in human whole blood using LC-MS/MS.
2016 (English)In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 119, p. 1-9Article in journal (Refereed) Published
Abstract [en]

The analgesic drug tramadol and its metabolites are chiral compounds, with the (+)- and (-)-enantiomers showing different pharmacological and toxicological effects. This novel enantioselective method, based on LC-MS/MS in reversed phase mode, enabled measurement of the parent compound and its three main metabolites O-desmethyltramadol, N-desmethyltramadol and N,O-didesmethyltramadol simultaneously. Whole blood samples of 0.5g were fortified with internal standards (tramadol-(13)C-D3 and O-desmethyl-cis-tramadol-D6) and extracted under basic conditions (pH 11) by liquid-liquid extraction. Chromatography was performed on a chiral alpha-1-acid glycoprotein (AGP) column preceded by an AGP guard column. The mobile phase consisted of 0.8% acetonitrile and 99.2% ammonium acetate (20mM, pH 7.2). A post-column infusion with 0.05% formic acid in acetonitrile was used to enhance sensitivity. Quantitation as well as enantiomeric ratio measurements were covered by quality controls. Validation parameters for all eight enantiomers included selectivity (high), matrix effects (no ion suppression/enhancement), calibration model (linear, weight 1/X(2), in the range of 0.25-250ng/g), limit of quantitation (0.125-0.50ng/g), repeatability (2-6%) and intermediate precision (2-7%), accuracy (83-114%), dilution integrity (98-115%), carry over (not exceeding 0.07%) and stability (stable in blood and extract). The method was applied to blood samples from a healthy volunteer administrated a single 100mg dose and to a case sample concerning an impaired driver, which confirmed its applicability in human pharmacokinetic studies as well as in toxicological and forensic investigations.

Keyword
Enantiomer; LC–MS/MS; N, O-didesmethyltramadol; N-desmethyltramadol; O-desmethyltramadol; Tramadol
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:liu:diva-125284 (URN)10.1016/j.jpba.2015.11.012 (DOI)000370211900001 ()26625281 (PubMedID)
Note

Funding agencies:The National Board of Forensic Medicine in Sweden funded this work.

Available from: 2016-02-19 Created: 2016-02-19 Last updated: 2017-11-30
Castaneto, M. S., Wohlfarth, A., Pang, S., Zhu, M., Scheidweiler, K. B., Kronstrand, R. & Huestis, M. A. (2015). Identification of AB-FUBINACA metabolites in human hepatocytes and urine using high-resolution mass spectrometry. Forensic Toxicology, 33(2), 295-310
Open this publication in new window or tab >>Identification of AB-FUBINACA metabolites in human hepatocytes and urine using high-resolution mass spectrometry
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2015 (English)In: Forensic Toxicology, ISSN 1860-8965, E-ISSN 1860-8973, Vol. 33, no 2, p. 295-310Article in journal (Refereed) Published
Abstract [en]

AB-FUBINACA, N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide, is an indazole synthetic cannabinoid identified in drug seizures around the world. Few metabolism data are available, despite the need for human urinary markers to detect AB-FUBINACA intake. Our main objective was to identify suitable analytical targets by analyzing human hepatocyte incubation samples with high-resolution mass spectrometry (HRMS) and to confirm the results in authentic urine specimens. We also determined AB-FUBINACAs metabolic stability in human liver microsomes (HLMs) and compared hepatocyte and urine results with in silico predictions. The metabolic stability of AB-FUBINACA was determined in pooled HLMs (1 A mu mol/l, up to 1 h). The metabolite profile of human hepatocytes (10 A mu mol/l, 1 and 3 h) and urine samples from two subjects were determined by HRMS using information-dependent tandem-mass spectrometry (MS-MS) acquisition. Data were analyzed with MetabolitePilot (TM) software utilizing different processing algorithms, including generic peak finding, mass defect filtering, neutral loss, and product ion filtering. In silico metabolite prediction was performed with MetaSite (TM) software. AB-FUBINACAs half-life in HLMs was 62.6 +/- A 4.0 min. AB-FUBINACA produced 11 metabolites (2 glucuronides) in human hepatocytes and 10 were identified in authentic human urine. Major metabolic pathways were terminal amide hydrolysis, acyl glucuronidation and hydroxylation at the aminooxobutane moiety. Epoxidation followed by hydrolysis, hydroxylation at the indazole moiety and dehydrogenation were minor pathways. Defluorination did not occur. Seventeen first-generation metabolites were predicted in silico, of which seven were observed in vitro and eight in vivo. We recommend AB-FUBINACA carboxylic acid, hydroxy AB-FUBINACA carboxylic acid, dihydrodiol AB-FUBINACA and dihydrodiol AB-FUBINACA carboxylic acid as suitable urinary markers.

Place, publisher, year, edition, pages
Springer Verlag (Germany), 2015
Keyword
AB-FUBINACA; Metabolite profiling; HRMS; Hepatocytes; In silico
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-120458 (URN)10.1007/s11419-015-0275-8 (DOI)000358055400010 ()
Note

Funding Agencies|National Institute on Drug Abuse, National Institutes of Health

Available from: 2015-08-12 Created: 2015-08-11 Last updated: 2017-12-04
Wohlfarth, A., Castaneto, M. S., Zhu, M., Pang, S., Scheidweiler, K. B., Kronstrand, R. & Huestis, M. A. (2015). Pentylindole/Pentylindazole Synthetic Cannabinoids and Their 5-Fluoro Analogs Produce Different Primary Metabolites: Metabolite Profiling for AB-PINACA and 5F-AB-PINACA. AAPS Journal, 17(3), 660-677
Open this publication in new window or tab >>Pentylindole/Pentylindazole Synthetic Cannabinoids and Their 5-Fluoro Analogs Produce Different Primary Metabolites: Metabolite Profiling for AB-PINACA and 5F-AB-PINACA
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2015 (English)In: AAPS Journal, ISSN 1550-7416, E-ISSN 1550-7416, Vol. 17, no 3, p. 660-677Article in journal (Refereed) Published
Abstract [en]

Whereas non-fluoropentylindole/indazole synthetic cannabinoids appear to be metabolized preferably at the pentyl chain though without clear preference for one specific position, their 5-fluoro analogs major metabolites usually are 5-hydroxypentyl and pentanoic acid metabolites. We determined metabolic stability and metabolites of N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide (AB-PINACA) and 5-fluoro-AB-PINACA (5F-AB-PINACA), two new synthetic cannabinoids, and investigated if results were similar. In silico prediction was performed with MetaSite (Molecular Discovery). For metabolic stability, 1 mu mol/L of each compound was incubated with human liver microsomes for up to 1 h, and for metabolite profiling, 10 mu mol/L was incubated with pooled human hepatocytes for up to 3 h. Also, authentic urine specimens from AB-PINACA cases were hydrolyzed and extracted. All samples were analyzed by liquid chromatography high-resolution mass spectrometry on a TripleTOF 5600+ (AB SCIEX) with gradient elution (0.1% formic acid in water and acetonitrile). High-resolution full-scan mass spectrometry (MS) and information-dependent acquisition MS/MS data were analyzed with MetabolitePilot (AB SCIEX) using different data processing algorithms. Both drugs had intermediate clearance. We identified 23 AB-PINACA metabolites, generated by carboxamide hydrolysis, hydroxylation, ketone formation, carboxylation, epoxide formation with subsequent hydrolysis, or reaction combinations. We identified 18 5F-AB-PINACA metabolites, generated by the same biotransformations and oxidative defluorination producing 5-hydroxypentyl and pentanoic acid metabolites shared with AB-PINACA. Authentic urine specimens documented presence of these metabolites. AB-PINACA and 5F-AB-PINACA produced suggested metabolite patterns. AB-PINACA was predominantly hydrolyzed to AB-PINACA carboxylic acid, carbonyl-AB-PINACA, and hydroxypentyl AB-PINACA, likely in 4-position. The most intense 5F-AB-PINACA metabolites were AB-PINACA pentanoic acid and 5-hydroxypentyl-AB-PINACA.

Place, publisher, year, edition, pages
American Association of Pharmaceutical Scientists, 2015
Keyword
5-fluoro-AB-PINACA; AB-PINACA; in silico prediction; metabolism; synthetic cannabinoids
National Category
Other Medical Sciences
Identifiers
urn:nbn:se:liu:diva-118859 (URN)10.1208/s12248-015-9721-0 (DOI)000353560700015 ()25721194 (PubMedID)
Note

Funding Agencies|Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health

Available from: 2015-06-08 Created: 2015-06-04 Last updated: 2017-12-04
Kechagias, S., Dernroth, D. N., Blomgren, A., Hansson, T., Isaksson, A., Walther, L., . . . Nystrom, F. H. (2015). Phosphatidylethanol Compared with Other Blood Tests as a Biomarker of Moderate Alcohol Consumption in Healthy Volunteers: A Prospective Randomized Study.. Alcohol and Alcoholism, 50(4), 399-406
Open this publication in new window or tab >>Phosphatidylethanol Compared with Other Blood Tests as a Biomarker of Moderate Alcohol Consumption in Healthy Volunteers: A Prospective Randomized Study.
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2015 (English)In: Alcohol and Alcoholism, ISSN 0735-0414, E-ISSN 1464-3502, Vol. 50, no 4, p. 399-406Article in journal (Refereed) Published
Abstract [en]

AIM: It is generally agreed that traditional alcohol biomarkers lack in sensitivity to detect hazardous alcohol consumption. The present study was undertaken to evaluate the ability of phosphatidylethanol (PEth) and traditional alcohol markers to detect moderate alcohol consumption and to distinguish between moderate alcohol consumption and abstinence.

METHODS: Forty-four subjects, 32 females and 12 males, were included in the study. They were randomized to alcohol abstention or to alcohol consumption. Female participants consumed 150 ml of red wine (equivalent to 16 g of alcohol) per 24 h and the male participants double the amount. The study lasted for 3 months. Blood samples were drawn at the start and at the end of the study period. Blood samples were analysed for PEth, carbohydrate-deficient transferrin (CDT), mean corpuscular volume (MCV), γ-glutamyltransferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT).

RESULTS: ROC curves for the various biochemical markers were plotted in order to assess their ability to discriminate between abstention and moderate daily consumption of alcohol. PEth and CDT were the only markers with AUROCs significantly higher than 0.5, and PEth was detected in all participants randomized to alcohol consumption.

CONCLUSION: PEth was the only marker that could detect moderate intake and the present results also indicate that PEth probably can distinguish moderate alcohol consumption from abstinence.

National Category
Substance Abuse
Identifiers
urn:nbn:se:liu:diva-119707 (URN)10.1093/alcalc/agv038 (DOI)000357867100005 ()25882743 (PubMedID)
Available from: 2015-06-24 Created: 2015-06-24 Last updated: 2017-12-04
Concheiro, M., Castaneto, M., Kronstrand, R. & Huestis, M. A. (2015). Simultaneous determination of 40 novel psychoactive stimulants in urine by liquid chromatography-high resolution mass spectrometry and library matching. Journal of Chromatography A, 1397, 32-42
Open this publication in new window or tab >>Simultaneous determination of 40 novel psychoactive stimulants in urine by liquid chromatography-high resolution mass spectrometry and library matching
2015 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1397, p. 32-42Article in journal (Refereed) Published
Abstract [en]

The emergence of novel psychoactive substances is an ongoing challenge for analytical toxicologists. Different analogs are continuously introduced in the market to circumvent legislation and to enhance their pharmacological activity. Although detection of drugs in blood indicates recent exposure and link intoxication to the causative agent, urine is still the most preferred testing matrix in clinical and forensic settings. We developed a method for the simultaneous quantification of 8 piperazines, 4 designer amphetamines and 28 synthetic cathinones and 4 metabolites, in urine by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Data were acquired in full scan and data dependent MS2 mode. Compounds were quantified by precursor ion exact mass, and confirmed by product ion spectra library matching, taking into account product ions exact mass and intensities. One-hundred pi, urine was subjected to solid phase cation exchange extraction (SOLA SCX). The chromatographic reverse-phase separation was achieved with gradient mobile phase of 0.1% formic acid in water and in acetonitrile in 20 min. The assay was linear from 2.5 or 5 to 500 mu g/L. Imprecision (n = 15) was less than15.4%, and accuracy (n = 15) 84.2-118.5%. Extraction efficiency was 51.2-111.2%, process efficiency 57.7-104.9% and matrix effect ranged from -41.9% to 238.5% (CV less than 23.3%, except MDBZP CV less than 34%). Authentic urine specimens (n = 62) were analyzed with the method that provides a comprehensive confirmation for 40 new stimulant drugs with specificity and sensitivity.

Place, publisher, year, edition, pages
Elsevier, 2015
Keyword
LC-HRMS; Novel psychoactive substance; Synthetic cathinones; Piperazines; Amphetamines; Urine
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:liu:diva-119231 (URN)10.1016/j.chroma.2015.04.002 (DOI)000355029300005 ()25931378 (PubMedID)
Note

Funding Agencies|Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health

Available from: 2015-06-15 Created: 2015-06-12 Last updated: 2017-12-04
Nilsson, G., Kugelberg, F., Ahlner, J. & Kronstrand, R. (2015). Validation of an LC-MS/MS method for the determination of zopiclone, N-desmethylzopiclone and 2-amino-5-chloropyridine in whole blood and its application to estimate the original zopiclone concentration in stored specimens. International journal of legal medicine (Print), 129(2), 269-277
Open this publication in new window or tab >>Validation of an LC-MS/MS method for the determination of zopiclone, N-desmethylzopiclone and 2-amino-5-chloropyridine in whole blood and its application to estimate the original zopiclone concentration in stored specimens
2015 (English)In: International journal of legal medicine (Print), ISSN 0937-9827, E-ISSN 1437-1596, Vol. 129, no 2, p. 269-277Article in journal (Refereed) Published
Abstract [en]

2-amino-5-chloropyridine (ACP) is a degradation product of zopiclone (ZOP) and may be formed when blood specimens are stored. ZOP instability in blood makes interpretation of concentrations difficult especially in cases of prolonged sample storage. This study investigated how ACP could be used to estimate the original concentration of ZOP in authentic samples. For that purpose, an analytical LC-MS/MS method for the quantitation of ACP, ZOP and the metabolite Ndesmethylzopiclone (NDZOP) in blood was validated. The method was then applied to investigate ACP formation, ZOP and NDZOP degradation in stored ZOP post-dosed authentic whole blood and two mathematical models were used to calculate the original concentration of ZOP. During storage, ACP was formed in amounts equimolar to the ZOP and NDZOP degradation. Results from samples in which ACP had been formed were used to test two models to estimate the original ZOP concentration. The correlation tests of the models showed strong correlations to the original ZOP concentration (r=0.960 and r=0.955) with p<0.01. This study showed that the equimolar degradation of ZOP and NDZOP to ACP could be used to estimate the original concentration of the unstable ZOP.

Place, publisher, year, edition, pages
Springer, 2015
Keyword
Degradation; Forensic toxicology; 2-amino-5-chloropyridine; Zopiclone; LC-MS/MS
National Category
Medical and Health Sciences Forensic Science
Identifiers
urn:nbn:se:liu:diva-105820 (URN)10.1007/s00414-014-1049-2 (DOI)000350032800007 ()25069820 (PubMedID)
Note

The article title of this article was in Manuscript: LC-MS/MS determination of 2-amino-5-chloropyridine to estimate the original zopiclone concentration in stored whole blood.

Available from: 2014-04-08 Created: 2014-04-08 Last updated: 2017-12-05Bibliographically approved
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