DETERMINATION OF NIFEDIPINE IN GINGIVAL CREVICULAR FLUID - A CAPILLARY GAS-CHROMATOGRAPHIC METHOD FOR NIFEDIPINE IN MICROLITER VOLUMES OF BIOLOGICAL FLUID

This paper describes a sensitive capillary gas chromatographic (GC) method for the determination of nifedipine in sub-microliter samples of gingival crevicular fluid (GCF) in order to assess if nifedipine is present in the GCF and if so, whether the local tissue concentrations of this drug are an important determinant in the development of gingival overgrowth. Liquid-liquid and solid-phase extraction were combined to give adequate sample clean-up and concentration for measurement by automated capillary GC with electron capture detection. Nifedipine and its principal metabolite, M-I, were analysed in both plasma and GCF in 9 adult male patients who had been taking nifedipine for over six months. M-I could not be measured in GCF. Plasma nifedipine and M-I levels were nomal, but the nifedipine levels found in the GCF of 7 patients (including all those with overgrowth) were remarkably elevated, 15 to 316-fold greater. This massive concentration of nifedipine into the GCF is therefore linked with gingival overgrowth. This is the first time that a GC method has been developed which permits determination of GCF pharmacokinetics of a drug which causes gingival overgrowth, and further investigation will lead to a better understanding of the tissue mechanisms involved.