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A sensitive quantitative assay for the determination of propafenone and two metabolites, 5-hydroxypropafenone and N-depropylpropafenone, in human K2EDTA plasma using LC-MS/MS with ESI operated in positive mode.
- Source :
-
Biomedical chromatography : BMC [Biomed Chromatogr] 2017 Oct; Vol. 31 (10). Date of Electronic Publication: 2017 May 07. - Publication Year :
- 2017
-
Abstract
- Propafenone is a potent antiarrhythmic agent; clinically propafenone has been used for a number of cardiac arrhythmias because it possesses multiple modes of action, via beta adrenergic receptor blockade and calcium antagonistic activity. Propafenone (PPF) exhibits extensive saturable presystemic biotransformation (first-pass effect) resulting in two active metabolites: 5-hydroxypropafenone (5-OH PPF) formed by CYP2D6 and N-depropylpropafenone (NDP) formed by both CYP3A4 and CYP1A2 enzymes. A specific and sensitive LC-MS/MS method was developed and validated for quantitation of PPF, 5-OH PPF and NDP using turboion spray in a positive ion mode. A solid-phase extraction was employed for the extraction from human plasma. Chromatographic separation of analytes was achieved using an ACE-5 C <subscript>8</subscript> (50 × 4.6 mm) column with a gradient mobile phase comprising ammonium acetate containing 0.01% TFA in purified water and acetonitrile. The retention times achieved were 1.36, 1.23, 1.24 min and 1.34 min for PPF, 5-OH PPF, NDP and IS (carbamazepine), respectively. Quantitation was performed by monitoring multiple reaction monitoring transition pairs of m/z 342.30 to m/z 116.20, m/z 358.30 to m/z 116.20, m/z 300.30 to m/z 74.20 and m/z 237.20 to m/z 194.10, respectively. The developed method was validated for various parameters. The calibration curves of PPF and 5-OH PPF showed linearity from 1 to 500 ng/mL, with a lower limit of quantitation of 1.0 ng/mL and for NDP linearity from 0.1 to 25 ng/mL with a lower limit of quantitation of 0.1 ng/mL. The bias and precision for intra- and-inter batch assays were <10 and 5%, respectively. The developed assay was used to evaluate pharmacokinetic properties of propafenone and its major metabolites in healthy human subjects.<br /> (Copyright © 2017 John Wiley & Sons, Ltd.)
- Subjects :
- Administration, Oral
Drug Stability
Edetic Acid
Humans
Limit of Detection
Linear Models
Propafenone administration & dosage
Propafenone chemistry
Propafenone pharmacokinetics
Reproducibility of Results
Chromatography, Liquid methods
Propafenone analogs & derivatives
Propafenone blood
Tandem Mass Spectrometry methods
Subjects
Details
- Language :
- English
- ISSN :
- 1099-0801
- Volume :
- 31
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Biomedical chromatography : BMC
- Publication Type :
- Academic Journal
- Accession number :
- 28261841
- Full Text :
- https://doi.org/10.1002/bmc.3967