C. Charette

Simultaneous determination of disopyramide and its mono-N-dealkyl metabolite in plasma and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic procedure is described for the determination of disopyramide and its mono-N-dealkyl metabolite which offers simplicity of extraction with excellent selectivity, sensitivity and reproducibility. The drug and metabolite, following basic diethyl ether extraction and back-extraction with acetic acid, are injected into a reversed-phase high-performance liquid chromatographic column and the absorbance of the eluate measured at 254 nm. Detectability limits of 0.05 micrograms/ml were obtained with both compounds, and studies of the reproducibility, precision, recovery, stability during storage and effect of time in separating plasma from erythrocytes are described. Applications of this high-performance liquid chromatographic procedure to plasma samples from patients on disopyramide therapy and to plasma and urine from a healthy dog administered single doses are reported.

Application of Statistical Moment Analysis to the Evaluation of Controlled Release Formulations

Riegelman and Collier have recently reviewed (1) the application of first moment analysis, also termed the mean residence time (MRT) method, to the evaluation ofin vivo absorption time using plasma concentration data following single dose administration. The object of the present report is to apply the MRT method, as well as conventional pharmacokinetic techniques, and to evaluate data derived from comparative bioavailability trials of controlled release formulations versus conventional products. The analyses were performed on data from single dose as well as from multiple dose studies conducted in our laboratories.