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Karlsson, Louise
Publications (10 of 14) Show all publications
Karlsson, L., Zackrisson, A. L., Josefsson, M., Carlsson, B., Green, H. & Kugelberg, F. . (2015). Influence of CYP2D6 and CYP2C19 genotypes on venlafaxine metabolic ratios and stereoselective metabolism in forensic autopsy cases.. The Pharmacogenomics Journal, 15(2), 165-71
Open this publication in new window or tab >>Influence of CYP2D6 and CYP2C19 genotypes on venlafaxine metabolic ratios and stereoselective metabolism in forensic autopsy cases.
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2015 (English)In: The Pharmacogenomics Journal, ISSN 1470-269X, E-ISSN 1473-1150, Vol. 15, no 2, p. 165-71Article in journal (Refereed) Published
Abstract [en]

We investigated whether polymorphisms in the CYP2D6 and CYP2C19 genes influence the metabolic ratios and enantiomeric S/R ratios of venlafaxine (VEN) and its metabolites O-desmethylvenlafaxine (ODV), N-desmethylvenlafaxine (NDV) and N,O-didesmethylvenlafaxine (DDV) in blood from forensic autopsy cases. In all, 94 postmortem cases found positive for VEN during toxicological screening were included. The CYP2D6 genotype was shown to significantly influence the ODV/VEN (P=0.003), DDV/NDV (P=0.010) and DDV/ODV (P=0.034) ratios. The DDV/ODV (P=0.013) and DDV/VEN (P=0.021) ratios were significantly influenced by the CYP2C19 genotype. The S/R ratios of VEN were significantly influenced by both CYP2D6 and CYP2C19 genotypes. CYP2D6 poor metabolizers (PMs) had lower S/R VEN ratios and CYP2C19 PMs had high S/R ratios of VEN in comparison. Our results show that the CYP2D6 genotype influences the O-demethylation whereas CYP2C19 influences the N-demethylation of VEN and its metabolites. In addition, we show a stereoselective metabolism where CYP2D6 favours the R-enantiomer whereas CYP2C19 favours the S-enantiomer.

National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:liu:diva-116540 (URN)10.1038/tpj.2014.50 (DOI)000351780200008 ()25245581 (PubMedID)
Available from: 2015-03-27 Created: 2015-03-27 Last updated: 2018-01-11
Karlsson, L., Andersson, M., Kronstrand, R. & Kugelberg, F. (2014). Mephedrone, Methylone and 3,4-Methylenedioxypyrovalerone (MDPV) Induce Conditioned Place Preference in Mice. Basic & Clinical Pharmacology & Toxicology, 115(5), 411-416
Open this publication in new window or tab >>Mephedrone, Methylone and 3,4-Methylenedioxypyrovalerone (MDPV) Induce Conditioned Place Preference in Mice
2014 (English)In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 115, no 5, p. 411-416Article in journal (Refereed) Published
Abstract [en]

During the last decade, there has been a worldwide increase in popularity and abuse of synthetic cathinones. Common ingredients of the so-called bath salts include mephedrone, methylone and 3,4-methylenedioxypyrovalerone (MDPV). Relatively little information about the pharmacology and addiction potential of these drugs is available. We used the conditioned place preference (CPP) paradigm to explore the reinforcing effects of three different synthetic cathinones. The primary aim of this study was to investigate whether mephedrone, methylone and MDPV induce CPP in mice. The secondary aims were to investigate a possible dose-response CPP and whether the synthetic cathinones induce higher CPP than amphetamine at equal dose. C57BL/6 mice were conditioned to mephedrone, methylone, MDPV and amphetamine at doses of 0.5, 2, 5, 10 or 20mg/kg (i.p.). During the conditioning, the mice received two training sessions per day for 4days. All four tested drugs showed a significant place preference compared with controls. Mice conditioned with MDPV (5 and 10mg/kg) displayed a greater preference score compared to mice conditioned with amphetamine (5 and 10mg/kg). Our findings show that mephedrone, methylone and MDPV produce CPP equal or higher than amphetamine strongly suggesting addictive properties. Given the public health concern of abuse, future pharmacological studies are necessary to fully understand the effects of these drugs.

Place, publisher, year, edition, pages
Wiley: 12 months, 2014
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-112616 (URN)10.1111/bcpt.12253 (DOI)000344015300006 ()24739011 (PubMedID)
Note

Funding Agencies|National Board of Forensic Medicine in Sweden; Forensic Science Center of Linkoping University; Lions Research Foundation

Available from: 2014-12-08 Created: 2014-12-05 Last updated: 2017-12-05
Karlsson, L., Green, H., Zackrisson, A. L., Bengtsson, F., Jakobsen Falk, I., Carlsson, B., . . . Kugelberg, F. (2013). ABCB1 gene polymorphisms are associated with fatal intoxications involving venlafaxine but not citalopram. International journal of legal medicine (Print), 127(3), 579-586
Open this publication in new window or tab >>ABCB1 gene polymorphisms are associated with fatal intoxications involving venlafaxine but not citalopram
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2013 (English)In: International journal of legal medicine (Print), ISSN 0937-9827, E-ISSN 1437-1596, Vol. 127, no 3, p. 579-586Article in journal (Refereed) Published
Abstract [en]

P-glycoprotein (P-gp), encoded by the ABCB1/MDR1 gene, is a drug transporter at the blood–brain barrier. Several polymorphisms in the ABCB1 gene are known to affect the activity and/or expression of P-gp, thereby influencing the treatment response and toxicity of P-gp substrates like citalopram and venlafaxine. In this study, we aimed to investigate the frequency of ABCB1 genotypes in forensic autopsy cases involving these two antidepressants. Further, the distribution of ABCB1 genotypes in deaths related to intoxication was compared to cases not associated to drug intoxication. The study included 228 forensic autopsy cases with different causes and manners of deaths. The ABCB1 single nucleotide polymorphisms (SNPs) G1199A, C1236T, C3435T and G2677T/A for these individuals were determined. The SNPs C1236T and C3435T in venlafaxine-positive cases were significantly different between the intoxication cases and non-intoxications. This was not seen for cases involving citalopram, indicating that the effect of genetic variants might be substrate specific. This novel finding should, however, be confirmed in future studies with larger number of cases.

Place, publisher, year, edition, pages
Springer Verlag (Germany), 2013
Keywords
ABCB1, Citalopram, Forensic material, Genotype, Postmortem, Venlafaxine
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-93390 (URN)10.1007/s00414-013-0849-0 (DOI)000318247100006 ()
Note

Funding Agencies|National Board of Forensic Medicine in Sweden||Swedish Research Council||

Available from: 2013-05-31 Created: 2013-05-31 Last updated: 2017-12-06Bibliographically approved
Boiso, S., Zackrisson, A. L., Jakobsen Falk, I., Karlsson, L., Carlsson, B., Tillmar, A., . . . Green, H. (2013). ABCB1 gene polymorphisms are associated with suicide in forensic autopsies. Pharmacogenetics & Genomics, 23(9), 463-469
Open this publication in new window or tab >>ABCB1 gene polymorphisms are associated with suicide in forensic autopsies
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2013 (English)In: Pharmacogenetics & Genomics, ISSN 1744-6872, E-ISSN 1744-6880, Vol. 23, no 9, p. 463-469Article in journal (Refereed) Published
Abstract [en]

Background Polymorphisms in ABCB1 have the ability to affect both the function and the expression of the transporter protein P-glycoprotein and may lead to an altered response for many drugs including some antidepressants and antipsychotics.Objective The aim of this study was to examine the impact of the ABCB1 polymorphisms 1199Gandgt;A, 1236Candgt;T, 2677Gandgt;T/A, and 3435Candgt;T in deaths by suicide.Patients and methods A total of 998 consecutive Swedish forensic autopsies performed in 2008 in individuals 18 years of age or older, where femoral blood was available and a toxicological screening had been performed, were investigated. Genotypes were assessed with pyrosequencing and information on the cause and manner of each death was obtained from the forensic pathology and toxicology databases.Results There was a significantly higher frequency of the T allele at positions 1236, 2677, and 3435 among the suicide cases compared with the nonsuicide cases.Conclusion Our result from forensic cases suggests that ABCB1 polymorphisms are associated with an increased risk for completed suicides. The biological mechanisms involved and the clinical implications for these findings are largely unknown and need to be examined further.

Place, publisher, year, edition, pages
Lippincott, Williams and Wilkins, 2013
Keywords
ABCB1, autopsy, forensic material, genotype, postmortem, sex, suicide
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-97235 (URN)10.1097/FPC.0b013e328363a9bf (DOI)000323220200002 ()
Note

Funding Agencies|National Board of Forensic Medicine in Sweden||Swedish Research Council||Swedish Cancer Society||

Available from: 2013-09-06 Created: 2013-09-05 Last updated: 2017-12-06
Karlsson, L., Carlsson, B., Hiemke, C., Ahlner, J., Bengtsson, F., Schmitt, U. & Kugelberg, F. C. (2013). Altered brain concentrations of citalopram and escitalopram in P-glycoprotein deficient mice after acute and chronic treatment. European Neuropsychopharmacology, 23(11), 1636-1644
Open this publication in new window or tab >>Altered brain concentrations of citalopram and escitalopram in P-glycoprotein deficient mice after acute and chronic treatment
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2013 (English)In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 23, no 11, p. 1636-1644Article in journal (Refereed) Published
Abstract [en]

Background: According to both in vitro and in vivo data P-glycoprotein (P-gp) may restrict the uptake of several antidepressants into the brain, thus contributing to the poor success rate of current antidepressant therapies. The therapeutic activity of citalopram resides in the Senantiomer, whereas the R-enantiomer is practically devoid of serotonin reuptake potency. To date, no in vivo data are available that address whether the enantiomers of citalopram and its metabolites are substrates of P-gp.

Methods: P-gp knockout (abcb1ab (-/-)) and wild-type (abcb1ab (+/+)) mice underwent acute (single-dose) and chronic (two daily doses for 10 days) treatment with citalopram (10 mg/kg) or escitalopram (5 mg/kg). Serum and brain samples were collected 1-6 h after the first or last i.p. injection for subsequent drug analysis by an enantioselective HPLC method. Results: In brain, 3-fold higher concentrations of S- and R-citalopram, and its metabolites, were found in abcb1ab (-/-) mice than in abcb1ab (+/+) mice after both acute and chronic citalopram treatments. After escitalopram treatment, the S-citalopram brain concentration was 3-5 times higher in the knockout mice than in controls.

Conclusions: The results provide novel evidence that the enantiomers of citalopram are substrates of P-gp. Possible clinical and toxicological implications of this finding need to be further elucidated.

Place, publisher, year, edition, pages
Elsevier, 2013
Keywords
Citalopram, enantiomers, escitalopram, mice knockout, P-glycoprotein
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-76122 (URN)10.1016/j.euroneuro.2013.01.003 (DOI)000328014700033 ()
Available from: 2012-03-28 Created: 2012-03-28 Last updated: 2017-12-07Bibliographically approved
Kingbäck, M., Karlsson, L., Zackrisson, A.-L., Josefsson, M., Carlsson, B., Bengtsson, F., . . . Kugelberg, F. C. (2012). Influence of CYP2D6 genotype on the disposition of the enantiomers of venlafaxine and its major metabolites in postmortem femoral blood. Forensic Science International, 214(1-3), 124-134
Open this publication in new window or tab >>Influence of CYP2D6 genotype on the disposition of the enantiomers of venlafaxine and its major metabolites in postmortem femoral blood
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2012 (English)In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 214, no 1-3, p. 124-134Article in journal (Refereed) Published
Abstract [en]

Venlafaxine (VEN) is an antidepressant drug mainly metabolized by the cytochrome P450 (CYP) enzyme CYP2D6 to the active metabolite O-desmethylvenlafaxine (ODV). VEN is also metabolized to N-desmetylvenlafaxine (NDV) via CYP3A4. ODV and NDV are further metabolized to N,O-didesmethylvenlafaxine (DDV). VEN is a racemic mixture of the S- and R-enantiomers and these have in vitro displayed different degrees of serotonin and noradrenaline reuptake inhibition. The aim of the study was to investigate if an enantioselective analysis of VEN and its metabolites, in combination with genotyping for CYP2D6, could assist in the interpretation of forensic toxicological results in cases with different causes of deaths. Concentrations of the enantiomers of VEN and metabolites were determined in femoral blood obtained from 56 autopsy cases with different causes of death. The drug analysis was done by liquid chromatography tandem mass spectrometry (LC/MS/MS) and the CYP2D6 genotyping by PCR and pyrosequencing. The mean (median) enantiomeric S/R ratios of VEN, ODV, NDV and DDV were 0.99 (0.91), 2.17 (0.93), 0.92 (0.86) and 1.08 (1.03), respectively. However, a substantial variation in the relationship between the S- and R-enantiomers of VEN and metabolites was evident (S/R ratios ranging from 0.23 to 17.6). In six cases, a low S/R VEN ratio (mean 0.5) was associated with a high S/R ODV ratio (mean 11.9). Genotyping showed that these individuals carried two inactive CYP2D6 genes indicating a poor metabolizer phenotype. From these data we conclude that enantioselective analysis of VEN and ODV can predict if a person is a poor metabolizer genotype/phenotype for CYP2D6. Knowledge of the relationship between the S- and R-enantiomers of this antidepressant drug and its active metabolite is also important since the enantiomers display different pharmacodynamic profiles.

Place, publisher, year, edition, pages
Elsevier, 2012
Keywords
CYP2D6; Enantiomers; Forensic toxicology; Postmortem toxicology; Venlafaxine
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-72238 (URN)10.1016/j.forsciint.2011.07.034 (DOI)000298634900032 ()21840145 (PubMedID)
Note

Funding agencies|Forensic Science Center of Linkoping University||National Board of Forensic Medicine in Sweden||Swedish Research Council| 2009-4740 |

Available from: 2011-11-23 Created: 2011-11-23 Last updated: 2017-12-08Bibliographically approved
Karlsson, L. (2012). P-glycoprotein and chiral antidepressant drugs: Pharmacokinetic, pharmacogenetic and toxicological aspects. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>P-glycoprotein and chiral antidepressant drugs: Pharmacokinetic, pharmacogenetic and toxicological aspects
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The blood-brain barrier (BBB) is formed by the capillary endothelial cells, joined together by tight junctions, with transporter proteins. BBB acts to regulate the brain concentrations of substances including many drugs. Transport across the cells is necessary for a drug to ensure that the drug reaches the site of action and transport proteins such as P-glycoprotein (P-gp; ABCB1) can limit the entrance into various tissues, including the brain.

Molecules that are not superimposable on their mirror images and thus exist in two enantiomeric forms (enantiomers) are said to be chiral. A racemic compound is one composed of a 50:50 mixture of two enantiomers, S- and R-enantiomers. Two examples of frequently prescribed racemic drugs are the chiral antidepressants venlafaxine (VEN) and citalopram (CIT). The enantiomers of VEN possess different pharmacodynamic profiles where the R-enantiomer is a potent inhibitor of both serotonin and noradrenaline reuptake (SNRI), while the S-enantiomer is more selective in inhibiting serotonin reuptake (SSRI). The SSRI effect of CIT resides in the S-enantiomer, whereas the R-enantiomer is considered to be therapeutically inactive, or even that it counteracts the effects. The S-enantiomer of CIT is now available as a separate SSRI (escitalopram, EsCIT). VEN and CIT are also among the most commonly found drugs in forensic autopsy cases.

Few previous studies have examined a possible enantioselective activity of P-gp. Thus, the general aim of this thesis was to study the enantiomeric distribution of chiral antidepressant drugs, focusing on the role of P-gp in the BBB. For this purpose, a mouse model disrupted of the genes coding for P-gp (abcb1ab (-/-) mice) was used. Brain and serum concentrations of the enantiomers of VEN and CIT, and their major metabolites, were compared to the corresponding wild-type mice (abcb1ab (+/+) mice). The open-field locomotor and rearing activities were examined after chronic VEN administration. In addition to the animal studies, genetic and toxicological aspects of P-gp were studied in a forensic autopsy material, where intoxication cases were compared with cases that were not related to intoxications.

The brain to serum concentration ratios for VEN, CIT and EsCIT differed between knockout mice and wild-type mice, with 2-3 fold higher brain concentrations in mice with no expression of P-gp. Hence, all studied drugs, and their major metabolites, were substrates for P-gp. There was no evidence for a stereoselective P-gp mediated transport. The P-gp substrate properties were reflected in the open-field behavior test where the knockout mice displayed increased center activity compared with wild-type mice following chronic VEN exposure. The genotype distribution of ABCB1 SNPs C1236T, G2677T and C3435T in VEN positive cases was significantly (or borderline) different between the intoxication cases and the non-intoxication cases. This difference in genotype distribution was not observed for the CIT positive cases.

To conclude, the present work has led to an increased knowledge about how the enantiomers of VEN and CIT are affected by the BBB transporter P-gp. Using an animal model, VEN and CIT have proved to be actively transported out of the brain by P-gp and no difference was observed for the enantiomers with regard to P-gp transport. Further, the ABCB1 genotype distribution was different in intoxication cases compared with non-intoxication cases. Taken together, these findings offer the possibility that the expression of P-gp in humans may be a contributing factor for limited treatment response and increased risk of side-effects following antidepressant drug treatment.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. p. 80
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1283
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-76126 (URN)978-91-7393-003-1 (ISBN)
Public defence
2012-04-13, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2012-03-28 Created: 2012-03-28 Last updated: 2012-03-28Bibliographically approved
Karlsson, L., Hiemke, C., Carlsson, B., Josefsson, M., Ahlner, J., Bengtsson, F., . . . Kugelberg, F. C. (2011). Effects on enantiomeric drug disposition and open-field behavior after chronic treatment with venlafaxine in the P-glycoprotein knockout mice model. Psychopharmacology, 215(2), 367-377
Open this publication in new window or tab >>Effects on enantiomeric drug disposition and open-field behavior after chronic treatment with venlafaxine in the P-glycoprotein knockout mice model
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2011 (English)In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 215, no 2, p. 367-377Article in journal (Refereed) Published
Abstract [en]

Our results show that P-gp at the blood-brain barrier plays an important role in limiting brain entry of the enantiomers of venlafaxine and its metabolites after chronic dosing. Taken together, the present pharmacokinetic and pharmacodynamic findings offer the possibility that the expression of P-gp in patients may be a contributing factor for limited treatment response.

Place, publisher, year, edition, pages
Springer, 2011
Keywords
abcb1ab . Blood–brain barrier . Knockout mice . P-glycoprotein . Pharmacodynamic . Pharmacokinetic .Venlafaxine
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-68038 (URN)10.1007/s00213-010-2148-5 (DOI)000289985700016 ()21191569 (PubMedID)
Note
The original publication is available at www.springerlink.com: Louise Karlsson, Christoph Hiemke, Björn Carlsson, Martin Josefsson, Johan Ahlner, Finn Bengtsson, Ulrich Schmitt and Fredrik C Kugelberg, Effects on enantiomeric drug disposition and open-field behavior after chronic treatment with venlafaxine in the P-glycoprotein knockout mice model., 2011, Psychopharmacology, (215), 2, 367-377. http://dx.doi.org/10.1007/s00213-010-2148-5 Copyright: Springer Science Business Media http://www.springerlink.com/Available from: 2011-05-06 Created: 2011-05-06 Last updated: 2017-12-11
Karlsson, L., Schmitt, U., Josefsson, M., Carlsson, B., Ahlner, J., Bengtsson, F., . . . Hiemke, C. (2010). Blood-brain barrier penetration of the enantiomers of venlafaxine and its metabolites in mice lacking P-glycoprotein. European Neuropsychopharmacology, 20(9), 632-640
Open this publication in new window or tab >>Blood-brain barrier penetration of the enantiomers of venlafaxine and its metabolites in mice lacking P-glycoprotein
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2010 (English)In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 20, no 9, p. 632-640Article in journal (Refereed) Published
Abstract [en]

According to in vitro studies the enantiomers of venlafaxine display different degrees of serotonin and noradrenaline reuptake inhibition. Therefore, clarification of the enantiomeric drug distribution between serum and brain is highly warranted. To elucidate if P-glycoprotein (P-gp) in a stereoselective manner transports venlafaxine and its metabolites out of the brain we used abcb1ab double-knockout mice that do not express P-gp. A single dose of racemic venlafaxine (10 mg/kg bw) was intraperitoneally injected to knockout (-/-) and wildtype (+/+) mice. Serum and brain samples were collected 1, 3, 6 and 9 h following drug administration for analysis by LC/MS/MS. One to six hours post-dose, the brain concentrations of venlafaxine, O-desmethylvenlafaxine and N-desmethylvenlafaxine were 2-3, 2-6 and 3-12 times higher in abcb1ab (-/-) mice compared to abcb1ab (+/+) mice, respectively. No major differences in the serum and brain disposition of the S- and R-enantiomers of venlafaxine and its metabolites were found between the groups. We conclude that P-gp decreases the penetration of the S- and R-enantiomers of venlafaxine and its major metabolites into the brain. No evidence of a stereoselective P-gp mediated transport of these substances was observed.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-58805 (URN)10.1016/j.euroneuro.2010.04.004 (DOI)20466523 (PubMedID)
Note
Original Publication: Louise Karlsson, Ulrich Schmitt, Martin Josefsson, Björn Carlsson, Johan Ahlner, Finn Bengtsson, Fredrik C Kugelberg and Christoph Hiemke, Blood-brain barrier penetration of the enantiomers of venlafaxine and its metabolites in mice lacking P-glycoprotein, 2010, European Neuropsychopharmacology, (20), 9, 632-640. http://dx.doi.org/10.1016/j.euroneuro.2010.04.004 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/ Available from: 2010-08-27 Created: 2010-08-27 Last updated: 2017-12-12
Kingbäck, M., Josefsson, M., Karlsson, L., Ahlner, J., Bengtsson, F., Kugelberg, F. C. & Carlsson, B. (2010). Stereoselective determination of venlafaxine and its three demethylated metabolites in human plasma and whole blood by liquid chromatography with electrospray tandem mass spectrometric detection and solid phase extraction. Journal of Pharmaceutical and Biomedical Analysis, 53(3), 583-590
Open this publication in new window or tab >>Stereoselective determination of venlafaxine and its three demethylated metabolites in human plasma and whole blood by liquid chromatography with electrospray tandem mass spectrometric detection and solid phase extraction
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2010 (English)In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 53, no 3, p. 583-590Article in journal (Refereed) Published
Abstract [en]

A stereoselective method is described for simultaneous determination of the S- and R-enantiomers of venlafaxine and its three demethylated metabolites in human plasma and whole blood samples. This validated method involved LC/MS/MS with positive electrospray ionization and solid phase extraction. Chromatographic separation was performed on a 250 mm x 2.1mm Chirobiotic V column with a total run time of 35 min. In plasma, calibration curves were in the range of 1-1000 nM for the S- and R-enantiomers of venlafaxine and O-desmethylvenlafaxine, and 0.5-500 nM for N-desmethylvenlafaxine and N,O-didesmethylvenlafaxine. In whole blood the corresponding concentrations were 10-4000 and 5-2000 nM, respectively. The intra-day precision was <6.3% and the inter-day precision was <9.9% for plasma and <15% and <19% for whole blood. LLOQ ranged between 0.25 and 0.5 nM. No ion suppression/enhancement or other matrix effects were observed. The method was successfully applied for determination of venlafaxine and its metabolites in plasma from patients and whole blood samples from forensic autopsy cases.

Keywords
Venlafaxine; Enantiomers; LC–ESI-MS/MS; Metabolites; Human
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-58798 (URN)10.1016/j.jpba.2010.03.043 (DOI)20435422 (PubMedID)
Available from: 2010-08-27 Created: 2010-08-27 Last updated: 2017-12-12
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