Novel and sensitive UPLC-MS/MS method for quantification of sofosbuvir in human plasma: application to a
Mamdouh R Rezk1, Emad B Basalious2, Mohammed E Amin3
1Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, 11562, Cairo, Egypt.
Biomedical Chromatography : BMC
|January 30, 2016
Summary
A new, sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method accurately measures sofosbuvir (SF) in human plasma. This rapid LC-MS/MS assay is suitable for bioequivalence studies, enabling high sample throughput.
Area of Science:
- Analytical Chemistry
- Pharmacokinetics
- Bioanalysis
Background:
- Accurate quantification of antiviral drugs like sofosbuvir (SF) is crucial for therapeutic drug monitoring and bioequivalence studies.
- Existing analytical methods may lack the sensitivity, speed, or efficiency required for high-throughput analysis of SF in biological matrices.
Purpose of the Study:
- To develop and validate a novel, sensitive, and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of sofosbuvir (SF) in human plasma.
- To establish a method suitable for application in bioequivalence studies, ensuring high sample throughput and reliable quantification.
Main Methods:
- A sensitive LC-MS/MS method was developed using a Xevo TQD system with electrospray ionization in multiple-reaction monitoring mode.
- Sample preparation involved tert-butyl methyl ether extraction, followed by chromatographic separation on an Acquity UPLC BEH C18 column.
- Method validation was conducted according to US Food and Drug Administration guidelines, assessing linearity, precision, and accuracy.
Main Results:
- The developed LC-MS/MS method demonstrated excellent linearity over the concentration range of 0.25–3500 ng/mL for SF.
- Intra- and inter-day precision and accuracy results were within acceptable regulatory limits.
- A rapid run time of 1 minute per sample allowed for the analysis of over 500 human plasma samples per day, with a very low quantification limit.
Conclusions:
- The developed and validated LC-MS/MS method is highly sensitive, accurate, and efficient for the determination of sofosbuvir in human plasma.
- The method's speed and low quantification limit make it ideal for large-scale bioequivalence studies, supporting drug development and regulatory submissions.
