Use of liquid chromatography-tandem mass spectrometry for foscarnet quantification in human serum and cerebrospinal fluid.

Abstract

Foscarnet (FCV) is used to treat cytomegalovirus, human herpesvirus, and human immunodeficiency virus infections. It is a low-molecular-weight compound containing carboxylate and phosphate groups. There are no reports on the use of liquid chromatography-tandem mass spectrometry (LC/MS/MS) to analyze FCV via bioanalysis. In the present study, we developed the ion-pair LC/MS/MS method to analyze FCV in human serum and cerebrospinal fluid (CSF). FCV was extracted from human serum and CSF by weak anion exchange (WAX) solid-phase extraction. The LC/MS/MS systems were coated with 0.1% phosphoric acid in methanol to avoid nonspecific absorption. FCV was detected using ion-pair LC/MS/MS with dibutylammonium acetate. Selected reaction monitoring transition of FCV in the negative ion mode was selected at m/z 125.1 → 62.9. FCV was selectively detected in human serum and CSF, and the liner range was 5-1000 μM (R2 = 0.99). The intraday and interday accuracy and precision were within ±15%. FCV was constantly extracted from human serum and CSF by WAX solid-phase extraction (recovery ratio = 76.0-77.9%). No matrix effect was observed. A robust LC/MS/MS method to analyze FCV was successfully developed. FCV was selectively measured using LC/MS/MS in very low extract volumes (20 μL). The method will be useful in evaluating the FCV level in human serum and CSF.