Quantitative analysis of terbinafine (Lamisil�) in human and minipig plasma by liquid chromatography tandem mass spectrometry

Abstract

A method using liquid chromatography/tandem mass spectrometry (LC/MS/MS) for the determination of terbinafine in human and minipig plasma has been developed and validated. The method used positive-ion mode for monitoring terbinafine, and used a stable isotope labelled terbinafine as the internal standard. Subsequent to acetonitrile protein precipitation, the supernatant was directly (unfiltered) injected onto the LC column (retention time approximately 4.3 min) for analysis. Interday and intraday accuracy and precision were assessed from the relative recoveries (observed concentration in percent of the nominal value) of spiked samples analyzed on three different days. The lower limit of quantitation (LLOQ) was 0.0679 ng/mL in human and minipig using a plasma sample volume of 0.08 mL. The method was fast, specific, and exhibited ruggedness. Furthermore, the use of turbulent flow chromatography (TurboFlow LC/MS/MS) coupled to mass spectrometry for direct analysis of terbinafine in plasma is discussed. The technique allowed direct introduction of plasma with satisfactory chromatographic peak shape and increased throughput.

High-throughput liquid chromatography for drug analysis in biological fluids: investigation of extraction column life

“…In some publications, the extraction column was reported to last approximately 300-600 injections for animal plasma samples [5][6][7]. In other published research papers, the lifetime of the extraction column was not mentioned at all [8,9]. Based on our experience, the extraction column did not perform well after as few as 160 human plasma sample injections (5-10 l direct plasma injection) when the traditional mobile phase (less than 1% of the acetic acid or formic acid in the water) was used.…”

“…Under these conditions, proteins and salts are flushed away while the small molecules are retained on the hydrophobic surface inside the porous particles [5][6][7][8][9][10][11][12]. The retained analytes are subsequently eluted from the extraction column using an organic mobile phase onto an analytical column for the chromatographic separation.…”

Direct analysis of eight chlorophenols in urine by large volume injection online turbulent flow solid-phase extraction liquid chromatography with multiple wavelength ultraviolet detection

“…Currently, this technique is mainly used for analysis of drugs and biomarkers. By using turbulent flow liquid chromatography tandem mass spectrometry (LC-MS/MS), the terbinafine in plasma have been directly analyzed, and the throughput was significantly improved [34]. The turbulent flow LC-MS/MS method was also successfully applied for simultaneous analysis of a broad range of controlled drugs in urine in a short cycle time [35].…”

Evaluation of online extraction/mass spectrometry for in vivo cassette analysis

“…Another approach, online extraction (OLE) has been widely used to reduce the sample preparation time. These techniques have employed polymerbased [12][13][14][15][16][17][18][19] or other restricted access media type columns [20,21] in conjunction with high flow rates/turbulent flow chromatography (TFC) to wash off matrix such as proteins while retaining the analyte on the column and subsequently eluting with a high organic mobile phase onto the MS.…”