Sensitive LC–MS/MS methods for the quantification of RGH-188 and its active metabolites, desmethyl- and didesmethyl-RGH-188 in human plasma and urine
| ISSN: | 0731-7085 |
|---|---|
| DOI: | 10.1016/j.jpba.2007.12.016 |
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f79a2668cdaaa2cd2154ebcd00884b40 https://doi.org/10.1016/j.jpba.2007.12.016 |
| Rights: | CLOSED |
| Přírůstkové číslo: | edsair.doi.dedup.....f79a2668cdaaa2cd2154ebcd00884b40 |
| Autor: | Gabriella Pásztor Mészáros, Éva Ágai-Csongor, Margit Kapás |
| Rok vydání: | 2008 |
| Předmět: |
Chromatography
Metabolite Clinical Biochemistry Selected reaction monitoring Pharmaceutical Science Desmethyl Mass spectrometry Sensitivity and Specificity High-performance liquid chromatography Piperazines Analytical Chemistry Matrix (chemical analysis) chemistry.chemical_compound Drug Stability chemistry Tandem Mass Spectrometry Calibration Drug Discovery Humans Quantitative analysis (chemistry) Spectroscopy Active metabolite Antipsychotic Agents Chromatography Liquid |
| Zdroj: | Journal of Pharmaceutical and Biomedical Analysis. 48:388-397 |
| ISSN: | 0731-7085 |
| DOI: | 10.1016/j.jpba.2007.12.016 |
| Popis: | Selective and sensitive LC-MS/MS methods have been developed and validated for simultaneous determination of RGH-188, a novel atypical antipsychotic, and its two active metabolites, desmethyl- and didesmethyl-RGH-188 in human plasma and urine. Deuterated analytes, [2H6]-RGH-188, [2H3]-desmethyl-RGH-188 and [2H8]-didesmethyl-RGH-188 were used as internal standards (IS). The compounds were isolated from the alkalized biological matrix using liquid-liquid extraction (LLE) and the extracts were analysed by reversed-phase HPLC with MS/MS detection. The chromatographic run time was 5.0min per injection. The PE Sciex API 365 mass spectrometer was equipped with a TurboIonSpray interface and operated in positive-ion, multiple reaction monitoring (MRM) mode. The mass transitions monitored were m/z 427.3-->382.2, 413.2-->382.2, 399.2-->382.2, 433.3-->382.2, 416.2-->382.2 and 407.3-->390.2 for RGH-188, desmethyl-RGH-188, didesmethyl-RGH-188, [2H6]-RGH-188, [2H3]-desmethyl-RGH-188 and [2H8]-didesmethyl-RGH-188, respectively. The lower limit of quantification (LLOQ) was 0.05 and 0.1ng/ml for RGH-188 and its metabolites, respectively, using 1ml of plasma. LLOQ in 1ml of urine was 0.1ng/ml for all three analytes. The methods were validated for selectivity, linearity, accuracy and precision. The lower limit of quantification, dilution integrity, matrix effect, stability of the analytes in the biological matrix during short- and long-term storage and after three freeze-thaw cycles were also tested. The assays were simple, specific and robust enough to support clinical development of RGH-188. |
| Databáze: | OpenAIRE |
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