Premium
Determination of terbinafine in human plasma using UPLC–MS/MS: Application to a bioequivalence study in healthy subjects
Author(s) -
Bhadoriya Abhaysingh,
Shah Priyanka A.,
Shrivastav Pranav S.,
Bharwad Kirtikumar D.,
Singhal Puran
Publication year - 2019
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4543
Subject(s) - chemistry , chromatography , terbinafine , bioequivalence , ammonium formate , high performance liquid chromatography , electrospray ionization , ethyl acetate , selected reaction monitoring , solvent , mass spectrometry , tandem mass spectrometry , bioavailability , pharmacology , antifungal , medicine , itraconazole , dermatology , organic chemistry
A high‐throughput and sensitive ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method has been developed for the determination of terbinafine in human plasma. The method employed liquid–liquid extraction of terbinafine and terbinafine‐d7 (used as internal standard) from 100 μL human plasma with ethyl acetate– n ‐hexane (80:20, v/v) solvent mixture. Chromatography was performed on a BEH C 18 (50 × 2.1 mm, 1.7 μm) column using acetonitrile–8.0 m m ammonium formate, pH 3.5 (85:15, v/v) under isocratic elution. For quantitative analysis, MS/MS ion transitions were monitored at m/z 292.2/141.1 and m/z 299.1/148.2 for terbinafine and terbinafine‐d7, respectively, using electrospray ionization in the positive mode. The method was validated according to regulatory guidance for selectivity, sensitivity, linearity, recovery, matrix effect, stability, dilution reliability and ruggedness with acceptable accuracy and precision. The method shows good linearity over the tested concentration range from 1.00 to 2000 ng/mL ( r 2 ≥ 0.9984). The intra‐batch and inter‐batch precision (CV) was 1.8–3.2 and 2.1–4.5%, respectively. The method was successfully applied to a bioequivalence study with 250 mg terbinafine in 32 healthy subjects. The major advantage of this method includes higher sensitivity, small plasma volume for processing and a short analysis time.