Determination of Pharmacokinetics Differences of Ammuxetine Isomers in Rat Plasma Using On-Line Solid Phase Extraction with Liquid Chrommatography-Tandem Mass Spectrometry
10.11895/j.issn.0253-3820.140771
- VernacularTitle:在线固相萃取-液相色谱串联质谱法测定阿姆西汀异构体的药代动力学差异
- Author:
Ying LI
;
Hang FENG
;
Wei GONG
;
Fanglin YU
;
Xiangyang XIE
;
Xinhua HE
;
Youzhi ZHANG
;
Xingguo MEI
- Publication Type:Journal Article
- Keywords:
On-line solid phase extraction-liquid chromatography-tandem mass spectrometry;
Isomers of ammuxetine;
Pharmacokinetics in rats;
Novel antidepressant
- From:
Chinese Journal of Analytical Chemistry
2014;(12):1717-1722
- CountryChina
- Language:Chinese
-
Abstract:
An on-line solid phase extraction ( SPE ) coupled with HPLC-MS/MS method was developed to determine S-ammuxetine and R-ammuxetine in rat plasma. The sample preparation consisted of the following steps:A protein precipitation extraction used methanol and acetonitrile ( 50:50 , V/V ); an on-line SPE treatment to remove most matrixes in plasma;an enrichment and separation step used a C18 analytical column. S-and R-ammuxetine were determined by tandem mass spectrometry. The SPE column was a Retain PEP Javelin (10 mm × 2. 1 mm × 5 μm), while the chromatographic separation was achieved using a ZORBAX SB-C18 (50 mm × 2. 1 mm × 3. 5 μm) analytical column with an isocratic mobile phase composed of acetonitrile-water-formic acid (40:60:0. 1, V/V/V, 0. 3 mL/min). The selected reaction monitoring mode of the positive ion was performed and the precursor to the product ion transitions of m/z 292 . 1/154 . 0 and m/z 260. 4/116. 2 were used to measure S-ammuxetine, R-ammuxetine and internal standard (propranolol). The method was linear over a concentration range from 0 . 2 to 1000 μg/L with the correlation coefficients of 0 . 9903 and 0 . 9951 . The average intra-day precision values were 1 . 2% -12 . 0% for S-ammuxetine and 0. 4%-11. 2% for R-ammuxetine, respectively. The average recoveries were 94. 2%-101. 6% for S-ammuxetine and 94. 3% -109. 4% for R-ammuxetine. Compared to the literature, the sensitivity of this method increased dramatically. The present method has been successfully applied to the preclinical rat research of ammuxetine isomers following intragastric administration.
