An improved high‐throughput liquid chromatographic/tandem mass spectrometric method for terbinafine quantification in human plasma, using automated liquid–liquid extraction based on 96‐well format plates

Abstract

A fully automated high-throughput liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed for terbinafine quantification in human plasma. The plasma samples were treated by liquid-liquid extraction (LLE) in 2.2 mL 96-deepwell plates. Terbinafine and the internal standard (IS) N-methyl-1-naphthalenemethylamine were extracted from human plasma by LLE, using a mixture of methyl t-butyl ether (MTBE)-hexane (70:30, v/v) as the organic solvent. All liquid transfer steps, including preparation of calibration standards and quality control samples, as well as the addition of the IS, were performed automatically by using robotic liquid handling workstations. After vortexing, centrifugation and freezing, the supernatant organic solvent was evaporated and reconstituted in a small volume of a reconstitution solution. Sample analysis was performed by reversed-phase LC-MS/MS, with positive ion electrospray ionization, using multiple reaction monitoring (MRM). The method had a very short sample preparation time and a chromatographic run time of 2.2 min. It was proved to have excellent sensitivity, specificity, accuracy as well as inter- and intraday precision for the quantification of terbinafine in human plasma. The calibration curve was linear for the range of concentrations 5.0-2000.0 ng/mL. The proposed method was applied to the rapid and reliable determination of terbinafine in a bioequivalence study after per os administration of 250 mg tablet formulations of terbinafine.

Extracting trace amount of terbinafine hydrochloride in biological fluids and wastewater samples using solid‐phase‐extraction based on magnetic nanoparticles followed by HPLC‐UV analysis

“…Comparison of the current work with the existing methods for the extraction and determination of terbinafine in the literature is indicated in Table . As can be seen in this table, large dynamic linear range and very low LOD and RSD were the significant features of the proposed method, which were comparable with or even better than LLE (requiring several time‐consuming manipulation steps) method that use very sensitive detection method such as HPLC‐UV or LC‐MS/MS (needing special training). Moreover, due to higher surface area‐to‐volume ratio and short diffusion route of the MNPs, extraction time of the proposed method was much shorter than that of other reported methods, leading to high sample throughout of the method in comparison with the other reported methods …”

“…At present, a number of analytical methods have been published for determining terbinafine raw material such as titrimetry in non‐aqueous solvent, voltammetry, ultraviolet (UV) spectrophotometric method, and capillary electrophoresis . Moreover, terbinafine has been determined in biological fluids by high‐performance liquid chromatography (HPLC) technique and microbiological bioassay . HPLC methods have also been used for determining the drug in tablet and cream forms .…”

“…Some separation/preconcentration procedures such as liquid–liquid extraction (LLE) and solid‐phase extraction (SPE) have been proposed for the extraction of terbinafine from biological samples, among which SPE procedures are considered superior to other procedures owing to their simplicity, consumption of small volumes of organic solvents, capability to eliminate undesirable matrix components, and ability to achieve a higher enrichment factor …”

Terbinafine: optimization of a LC method for quantitative analysis in pharmaceutical formulations and its application for a tablet dissolution test

“…[6][7][8][9][10] Also, TBF has been determined in biological fluids by HPLC technique and microbiological bioassays. [11][12][13][14][15] Another HPLC method has been used to determine the drug in tablets and creams. 16 However, there is a lack of information concerning both the quantitation of TBF in pharmaceutical solution dosage forms and the dissolution test of TBF from tablet dosage forms.…”

Changing need for bioanalysis during drug development

“…Over the past few decades, a plethora of assays has been continuously developed for new chemical entities (NCEs) to support various stages of discovery and development, including assays for important metabolites (Satonin et al, 2007;Zeng et al, 2007;He et al, 2007;Chawla et al, 2006). Additionally, multiple analytical procedures are available for prescription medicines (Rx) and/or generic products (Basha et al, 2007;Link et al, 2007;Oostendorp et al, 2007;Kiel et al, 2007;Wang et al, 2006;Dotsikas et al, 2007;Nirogi et al, 2007;Venkatesh et al, 2006;Pavan Kumar et al, 2006;Pasha et al, 2006). Needless to say, all of the above document the importance of bioanalytical aspects not only during discovery and development of NCEs but also during the post approval period.…”