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Quantitative determination of LY‐404,039, a metabotropic glutamate 2/3 receptor agonist, in rat plasma using chemical derivatization and HPLC–MRM/MS.
- Source :
- Biomedical Chromatography; Sep2022, Vol. 36 Issue 9, p1-9, 9p
- Publication Year :
- 2022
-
Abstract
- A rapid, selective and sensitive method was developed and validated for the determination of LY‐404,039 concentration in rat plasma using a butylation derivatization step to improve chromatographic characteristics and enhance signal intensity. The method consisted of a protein precipitation extraction followed by derivatization with butanol/HCl and analysis by high‐performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS). The separation was achieved using a 100 × 2.1 mm (2.6 μm) Thermo Scientific Accucore RP‐MS column combined with an isocratic mobile phase composed of 40:60 acetonitrile–0.1% formic acid in water. An analytical range of 2.0–1,000 ng/ml was validated and used to quantify LY‐404,039 in rat plasma. The novel method met all of the requirements of specificity, sensitivity, linearity, precision, accuracy and stability. A pharmacokinetic study was performed in rats and the novel analytical method was used as a routine analysis method to provide enhanced measurements of plasma concentrations of LY‐404,039. The plasma pharmacokinetic results indicate very short terminal half‐life (0.27 h ± 0.8) and high clearance (0.97 L/h/kg ± 0.12), suggesting that LY‐404,039 is rapidly eliminated in the rat. Dose‐dependent pharmacokinetics were observed following subcutaneous administration of LY‐404,039 at doses of 0.1, 0.3 and 1.0 mg/kg. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02693879
- Volume :
- 36
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- Biomedical Chromatography
- Publication Type :
- Academic Journal
- Accession number :
- 158529518
- Full Text :
- https://doi.org/10.1002/bmc.5423