MEASUREMENT OF AZACYCLONOL IN URINE AND SERUM OF HUMANS FOLLOWING TERFENADINE (SELDANE) ADMINISTRATION USING GAS-CHROMATOGRAPHY MASS-SPECTROMETRY

A gas chromatographic-mass spectrometric (GC-MS) method is presented for the analysis of azacyclonol (AZA), a metabolite of terfenadine in serum and urine specimens. Following an alkaline extraction, AZA and an internal standard were derivatized using heptafluorobutyric anhydride. Fourier transform infrared spectrometry suggested that two sites on the AZA molecule were derivatized. GC-MS of the extracts had a limit of quantitation (LOQ) of 1 ng/ml and linear range of 1-1000 ng/ml in urine. Four volunteers were administered a therapeutic regimen of terfenadine followed by urine and serum specimen collection(s) during the next seven days. The results indicated that following a 60-mg dose of terfenadine each 12 h for five days, (1) AZA appears in urine within 2 h, (2) urine AZA concentrations were above the LOQ 72 h following the last dose, (3) peak urine concentrations were as high as 19 000 ng/ml, and (4) mean serum concentration following the ninth dose was 59 ng/ml.