Enantioselective analysis of unbound tramadol, O-desmethyltramadol and N-desmethyltramadol in plasma by ultrafiltration and LC-MS/MS: application to clinical pharmacokinetics
- PMID: 22173007
- DOI: 10.1016/j.jchromb.2011.11.033
Enantioselective analysis of unbound tramadol, O-desmethyltramadol and N-desmethyltramadol in plasma by ultrafiltration and LC-MS/MS: application to clinical pharmacokinetics
Abstract
This study describes the enantioselective analysis of unbound and total concentrations of tramadol and its main metabolites O-desmethyltramadol (M1) and N-desmethyltramadol (M2) in human plasma. Sample preparation was preceded by an ultrafiltration step to separate the unbound drug. Both the ultrafiltrate and plasma samples were submitted to liquid/liquid extraction with methyl t-butyl ether. Separation was performed on a Chiralpak(®) AD column and tandem mass spectrometry consisting of an electrospray ionization source, positive ion mode and multiple reaction monitoring was used as the detection system. Linearity was observed in the following ranges: 0.2-600 and 0.5-250 ng/mL for analysis of total and unbound concentrations of the tramadol enantiomers, respectively, and 0.1-300 and 0.25-125 ng/mL for total and unbound concentrations of the M1 and M2 enantiomers, respectively. The lower limits of quantitation were 0.2 and 0.5 ng/mL for analysis of total and unbound concentration of each tramadol enantiomer, respectively, and 0.1 and 0.25 ng/mL for total and unbound concentrations of M1 and M2 enantiomers, respectively. Intra- and interassay reproducibility and inaccuracy did not exceed 15%. Clinical application of the method to patients with neuropathic pain showed plasma accumulation of (+)-tramadol and (+)-M2 after a single oral dose of racemic tramadol. Fractions unbound of tramadol, M1 or M2 were not enantioselective in the patients investigated.
Copyright © 2011 Elsevier B.V. All rights reserved.
Similar articles
-
HPLC-UV assay of tramadol and O-desmethyltramadol in human plasma containing other drugs potentially co-administered to participants in a paediatric population pharmacokinetic study.J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Nov 1;1184:122971. doi: 10.1016/j.jchromb.2021.122971. Epub 2021 Oct 7. J Chromatogr B Analyt Technol Biomed Life Sci. 2021. PMID: 34649173 Review.
-
Analysis of total and unbound hydromorphone in human plasma by ultrafiltration and LC-MS/MS: application to clinical trial in patients undergoing open heart surgery.J Pharm Biomed Anal. 2012 Dec;71:63-70. doi: 10.1016/j.jpba.2012.07.025. Epub 2012 Jul 31. J Pharm Biomed Anal. 2012. PMID: 22884788 Clinical Trial.
-
Determination of total and unbound sufentanil in human plasma by ultrafiltration and LC-MS/MS: application to clinical pharmacokinetic study.J Pharm Biomed Anal. 2012 Jul;66:306-13. doi: 10.1016/j.jpba.2012.03.050. Epub 2012 Apr 3. J Pharm Biomed Anal. 2012. PMID: 22522038
-
Simultaneous analysis of tramadol, O-desmethyltramadol, and N-desmethyltramadol enantiomers in rat plasma by high-performance liquid chromatography-tandem mass spectrometry: application to pharmacokinetics.Chirality. 2011 Apr;23(4):287-93. doi: 10.1002/chir.20914. Epub 2010 Nov 29. Chirality. 2011. PMID: 21384434
-
Quantification in postmortem blood and identification in urine of tramadol and its two main metabolites in two cases of lethal tramadol intoxication.J Anal Toxicol. 2010 Nov;34(9):599-604. doi: 10.1093/jat/34.9.599. J Anal Toxicol. 2010. PMID: 21073815 Review.
Cited by
-
Pharmacokinetic profile of injectable tramadol in the koala (Phascolarctos cinereus) and prediction of its analgesic efficacy.PLoS One. 2021 Mar 3;16(3):e0247546. doi: 10.1371/journal.pone.0247546. eCollection 2021. PLoS One. 2021. PMID: 33657107 Free PMC article.
-
LC-MS/MS Quantification of Tramadol and Gabapentin Utilizing Solid Phase Extraction.Int J Anal Chem. 2018 Oct 28;2018:1605950. doi: 10.1155/2018/1605950. eCollection 2018. Int J Anal Chem. 2018. PMID: 30510578 Free PMC article.
-
Chiral Drug Analysis in Forensic Chemistry: An Overview.Molecules. 2018 Jan 28;23(2):262. doi: 10.3390/molecules23020262. Molecules. 2018. PMID: 29382109 Free PMC article. Review.
-
Largazole pharmacokinetics in rats by LC-MS/MS.Mar Drugs. 2014 Mar 20;12(3):1623-40. doi: 10.3390/md12031623. Mar Drugs. 2014. PMID: 24658499 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources