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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.

Authors:
Mohammad Taher Bahrami Bahareh Mohammadi Shahram Miraghaei Atefeh Babaei Matin Ghaheri Gholamreza Bahrami

J Sep Sci 2016 Jul 6;39(14):2702-9. Epub 2016 Jul 6.

School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.

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.

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http://dx.doi.org/10.1002/jssc.201501375DOI Listing
July 2016

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