title: Intracerebral microdialysis coupled to LC-MS/MS for the determination tramadol and its major pharmacologically active metabolite O-desmethyltramadol in rat brain microdialysates.
abstract: A rapid and sensitive method involving liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS) coupled to an intracerebral microdialysis technique was developed for the determination and pharmacokinetic investigation of tramadol and its major active metabolite O-desmethyltramadol (ODT) in rat brain. The microdialysis samples were separated on a C18 column and eluted with a mobile phase of acetonitrile-water-formic acid (50:50:0.1; v/v/v) at a flow rate of 0.3 mL/min. The ESI-MS/MS spectra were performed in electrospray positive ion mode, and the analytes were detected by multiple reaction monitoring (MRM) of the transitions m/z [M + H]+264.3 → 58.2 for tramadol, m/z [M + H]+250.3 → 58.3 for ODT, and m/z [M + H]+379.4 → 264.0 for ambroxol (internal standard; IS). The total run time was 4.0 min. A lower limit of quantitation (LLOQ) was achieved as 1 ng/mL for tramadol and 0.5 ng/mL for ODT, with excellent linearity over a concentration range of 1 ~ 500 ng/mL (r > 0.99) for tramadol and 0.5 ~ 50 ng/mL for ODT (r > 0.99), respectively. The proposed method was successfully applied to the pharmacokinetic studies of tramadol and ODT in rat brain. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Department of Pharmacology, Basic Medical School of Wuhan University, No. 185 Donghu Road, Wuhan, 430071, China.
authors.forename: Mingzhou
authors.identifier: http://orcid.org/0000-0002-7265-3356
authors.initials: M
authors.lastname: Liu
authors.affiliation: Inspection & Quarantine Technical Center, Hubei Entry-Exit Inspection Quarantine Bureau, No. 588 Qintai Road, Wuhan, 430050, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Basic Medical School of Wuhan University, No. 185 Donghu Road, Wuhan, 430071, China.
authors.forename: Xuming
authors.initials: X
authors.lastname: Yu
authors.affiliation: School of Biological Sciences, Baotou Teachers' College of Inner Mongolia University of Science and Technology, No. 3 of Kexue Street, Qingshan District, Baotou, 014030, China.
authors.forename: Guicheng
authors.initials: G
authors.lastname: Dong
authors.affiliation: Department of Pharmacology, Basic Medical School of Wuhan University, No. 185 Donghu Road, Wuhan, 430071, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Yue
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D057230:Limit of Detection; D008297:Male; D017551:Microdialysis / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014147:Tramadol / Q000031:analogs & derivatives* / Q000032:analysis / Q000134:cerebrospinal fluid* / Q000378:metabolism
chemical_list: C080580:O-demethyltramadol; D014147:Tramadol
keywords: LC-ESI-MS/MS; O-desmethyltramadol; microdialysis; pharmacokinetics; tramadol