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.

Centrally administered CYP2D inhibitors increase oral tramadol analgesia in rats

“…Tramadol, ODSMT, NDSMT, and their isotopomers, tramadol-D 3 -13 C, Odesmethyltramadol-D 6 and N-desmethyltramadol-D 3 were analyzed by LC-ESI-MS/MS assay adapted from previously published methods (Verplaetse and Tytgat, 2012, Tanaka et al, 2016, Liu et al, 2017. Agilent 1260 LC system, coupled with Agilent 6430 Triple Quadrupole system (Agilent Technologies) was used.…”

Development of a novel LC–MS/MS method for detection and quantification of tramadol hydrochloride in presence of some mislabeled drugs: Application to counterfeit study

“…A literature survey revealed that several methods have been reported for the determination of TRM either alone or in the presence of other co‐formulated materials. These include spectrophotometric (Abdellatef, ; Amin, Adawy, Ali, & El‐Shahatt, ; Dhumal, Bhusari, Ghante, & Jain, ; Glavanović, Glavanović, & Tomišić, ; Lakshmi, Ravisankar, Kumar, & Babu, ; Thomas & Sankar, ), spectrofluorimetric (Abdellatef, El‐Henawee, El‐Sayed, & Ayad, ; Smith, Manavalan, Kannan, & Rajendiran, ), chromatographic (Baconi, Stan, Abdul Jalil Ebrahim, Tuchila, & Balalau, ; Batool, Ahmed, & Rasheed, ; Desai, Captain, & Kamdar, ; Dhumal, Bhusari, Patra, Thareja, & Jain, ; Karunakaran, Navaneethan, & Elango, ; Kiarostami, Rouini, Mohammadian, Lavasani, & Ghazaghi, ; Ravisankar, Sridevi, & Kumari, ; Solomon, Anand, Shukla, Sivakumar, & Venkatnarayanan, ), electrochemical (Chitravathi & Munichandraiah, ; Deiminiat, Rounaghi, & Arbab‐Zavar, ; Fakhari, Sahragard, Ahmar, & Tabani, ; Ganjali, Razavi, Faridbod, Riahi, & Norouzi, ; Madrakian, Alizadeh, Bahram, & Afkhami, ) and electrophoresis (Cunha, Ribeiro, Muñoz, & Richter, ) methods in addition to the hyphenated methods where the chromatographic separations are coupled with the detection (El‐Sayed, Mohamed, Nasser, Button, & Holt, ; Haage, Kronstrand, Carlsson, Kugelberg, & Josefsson, ; Liu, Wang, Yu, Dong, & Yue, ; Tambe, Deodhar, & Prakya, ; Tanaka, Naito, Mino, & Kawakami, ; Yilmaz & Erdem, ). Thus, the aim of the present study was to develop a highly sensitive, rapid and accurate LC–MS/MS method for simultaneous quantitation of TRM and some expected co‐formulated compounds.…”