HIGH-PRESSURE LIQUID-CHROMATOGRAPHIC ASSAY OF THEOPHYLLINE IN DOG FECES FOLLOWING ORAL-ADMINISTRATION OF SUSTAINED-RELEASE PRODUCTS

A solid-phase-extraction reversed-phase HPLC assay is described for th e determination of theophylline embedded in dog feces as powder, susta ined-release tablets, or capsules. The feces is extracted with 5% isop ropyl alcohol in chloroform in the presence of beta-hydroxypropyl-theo phylline as the internal standard. Separation and quantitation are ach ieved with a C18 analytical column. UV absorbance is monitored at 280 nm. Recovery of theophylline was >50%. The assay is linear between 1 0 and 400 mg amounts of theophylline in 50 g of feces. Inter- and intra day coefficients of variation of the chromatographic assay were <3%, a nd the extraction procedure was highly reproducible with coefficients of variation of <10% at amounts of drug from 1 0 to 400 mg. By keeping the stool/solvent extraction ratio constant, the method is equally ef fective in extracting theophylline from different sizes of stool sampl es (50 versus 200 g of stool). The assay was applied to evaluate the t heophylline content in feces following oral administration of the drug to dogs as tablet (Theo-Dur) and capsule (Slo-Bid) dosage forms. The resulting fecal recovery values of each product were inversely related to the corresponding bioavailability values obtained from the literat ure.