Quantification of sofosbuvir in human serum by liquid chromatography with negative ionization mass spectrometry using the parent peak and its source-induced fragment: Application to a bioequivalence study

In the mass spectrometry of sofosbuvir, a new orally administered antihepatitis C drug, a weak peak is detected at the m/z value of the parent ion (m/z 530) as a result of in‐source dissociation and current methods to its quantification, is based on monitoring of the parent peak using ultra high‐per...

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Bibliographic Details
Published in:Journal of separation science 2016-07, Vol.39 (14), p.2702-2709
Main Authors: Bahrami, Mohammad Taher, Mohammadi, Bahareh, Miraghaei, Shahram, Babaei, Atefeh, Ghaheri, Matin, Bahrami, Gholamreza
Format: Article
Language:English
Subjects:
Antiviral drugs
Bioequivalence study
Chromatography
Chromatography, Liquid
Drugs
Error analysis
Fragmentation
Hepatitis
Humans
Mass spectrometry
Molecular Conformation
Monitoring
Parents
Pharmacology
Serums
Sofosbuvir
Sofosbuvir - blood
Source-induced dissociation
Spectrometry, Mass, Electrospray Ionization
Tandem Mass Spectrometry
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Summary:In the mass spectrometry of sofosbuvir, a new orally administered antihepatitis C drug, a weak peak is detected at the m/z value of the parent ion (m/z 530) as a result of in‐source dissociation and current methods to its quantification, is based on monitoring of the parent peak using ultra high‐performance liquid chromatography with tandem mass spectrometry. With these methods serum concentration of the drug is quantifiable only up to 4–5 h postdose. However, the fragmentation of the molecule generates a more stable ion at m/z 287 (base peak) with a signal intensity of about tenfold compared to the parent ion. Our study was aimed to improve sensitivity of analysis by acquisition of the m/z value of the daughter ion from which it originated instead of the parent molecule. This novelty allows us to measure serum concentrations of the drug for a longer time postdose and provides more opportunity for pharmacokinetic studies of sofosbuvir. Our method was linear over the concentration range of 2–2560 ng/mL of sofosbuvir in human serum with a limit of quantification of 2 ng/mL compared to 10 ng/mL reported previously. The coefficient variation values of both inter and intraday analysis were less than 13.8%, and the percentage error was less than 6.3.
ISSN:1615-9306
1615-9314
DOI:10.1002/jssc.201501375