| Title | LC-MS/MS determination of carbamathione in microdialysis samples from rat brain and plasma. | | Author(s) | Kaul S, Williams TD, Lunte CE, Faiman MD | | Institution | Ralph N. Adams Institute for Bioanalytical Chemistry, Department of Chemistry, University of Kansas, Lawrence, KS 66045, USA. | | Source | J Pharm Biomed Anal 2009 Jul 30. | | Abstract | A selective liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of S-(N, N-diethylcarbamoyl) glutathione (carbamathione) in microdialysis samples from rat brain and plasma. S-(N, N-Diethylcarbamoyl) glutathione (carbamathione) is a metabolite of disulfiram. This metabolite may be responsible for disulfiram's effectiveness in the treatment of cocaine dependence. Chromatographic separations were carried out on an Alltech Altima C-18 (50mm longx2.1mm i.d., 3mum particles) analytical column at a flow rate of 0.3ml/min. Solvent A consisted of 10mM ammonium formate, methanol, and formic acid (99:1:0.06, v/v/v). Solvent B consisted of methanol, 10mM ammonium formate and formic acid (99:1:0.06, v/v/v). A 20min linear gradient from 95% aqueous to 95% organic was used. Tandem mass spectra were acquired on a Micromass Quattro Ultima "triple" quadrupole mass spectrometer equipped with an ESI interface. Quantitative mass spectrometric analysis was conducted in positive ion mode selected reaction monitoring (SRM) mode looking at the transition of m/z 407-100 and 175 for carbamathione and m/z 392-263 for the internal standard S-hexyl glutathione. The simultaneous collection of microdialysate from blood and brain was used to monitor carbamathione concentrations centrally and peripherally. Good linearity was obtained over a concentration range of 0.25-10,000nM. The lowest limit of quantification (LLOQ) was determined to be 1nM and the lowest limit of detection (LLOD) was calculated to be 0.25nM. Intra- and inter-day accuracy and precision were determined and for all the samples evaluated, the variability was less that 10% (R.S.D.). | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19709836 |
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