A rapid and sensitive liquid chromatography/tandem mass spectrometry assay for simultaneous quantitation of disopyramide and its major metabolite, mono-isopropyl-disopyramide, in rat plasma and its application to a pharmacokinetic study.
J Chromatogr B Analyt Technol Biomed Life Sci
; 1096: 154-159, 2018 Oct 01.
Article
in En
| MEDLINE
| ID: mdl-30173081
ABSTRACT
Disopyramide as an antiarrhythmic agent has been used for treating ventricular tachycardia and metabolized into its major metabolite, mono-isopropyl-disopyramide, by CYP3A4. We developed a novel, selective, highly sensitive, accurate, rapid method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of disopyramide and mono-isopropyl-disopyramide in rat plasma. This study is the first report for the assay validation using LC-MS/MS in biological fluids after simple protein-precipitation method. The most sensitive signals by multiple reaction monitoring (MRM) showed at m/z 340.2â¯ââ¯239.2 and 298.2â¯ââ¯239.2 with same fragment ion for disopyramide and mono-isopropyl-disopyramide, respectively. The lower limit of quantification (LLOQ) was determined at 2â¯ng/mL for both analytes and the linear concentration ranges were found to be 2-2000â¯ng/mL for disopyramide and 2-1000â¯ng/mL for mono-isopropyl-disopyramide. Finally, this assay was successfully applied to pharmacokinetic analysis of disopyramide and mono-isopropyl-disopyramide after oral and intravenous administration of disopyramide.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chromatography, Liquid
/
Disopyramide
/
Tandem Mass Spectrometry
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Chromatogr B Analyt Technol Biomed Life Sci
Journal subject:
ENGENHARIA BIOMEDICA
Year:
2018
Document type:
Article