Analytical methods for the determination of terbinafine and its metabolites in human plasma, milk and urine.
Analytical procedures have been developed for the determination of the allylamine antimycotic terbinafine (1) and its demethylderivate (2) in plasma, milk and urine, and the metabolite carboxy-terbinafine (3) in plasma and urine, as well as the further metabolites demethyl-carboxy-terbinafine (4) and naphthoic acid (5) in urine. HPLC-methods for plasma analysis employed either electrochemical detection (for 1 and 2) or UV-detection (for 3) following a protein precipitation step with methanol or sample extraction with hexane as appropriate. For quantitative urine analysis of substances 1-4 native urine samples were deconjugated, mixed with internal standard and injected by an autosampler into a microprocessor controlled HPLC-system. The substances were monitored by UV-absorption. The metabolite 5 was determined in urine after deconjugation, sample preparation with commercially available cartridges and silylation by automatized GC with fused silica capillary column and FID-detection. The standard calibration curves for the parent compound (1) and metabolites (2-5) are linear within the required analytical ranges. The detection limit for 1 and 2 is 50 ng/ml in plasma and 150 ng/ml in milk and for 3 in plasma 100 ng/ml. The detection limit in urine is 300 ng/ml for all substances (1-4) analyzed by HPLC and 50 ng/ml for 5 analyzed by GC.
Schatz
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Sandoz Forschungsinstitut, Vienna, Austria.
Haberl
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D000935:Antifungal Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001711:Biotransformation; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D008895:Milk, Human / Q000378:metabolism*; D009281:Naphthalenes / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000077291:Terbinafine
D000935:Antifungal Agents; D007202:Indicators and Reagents; D009281:Naphthalenes; D000077291:Terbinafine