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An automated method utilizing laboratory robotics has been developed for quantifying diclofenac sodium concentrations in human plasma. The robotic system aliquots the biological sample, adds the internal standard (CGP 4287), extracts the compounds from the acidified biological matrix (pH less than 2) into an organic phase (hexane-isopropyl alcohol), and concentrates the extracts for reversed-phase, high-performance liquid chromatographic (HPLC) analysis. The laboratory robot is directly interfaced to the HPLC system, and the data are automatically collected and results calculated. Separation is achieved on a 3-microns ODS (6.2-mm x 8.0-cm) column with ultraviolet (UV) detection of the drug and internal standard at 280 nm. Recovery and reproducibility assessments indicate good accuracy (overall mean relative recovery of 99.8%) and precision (coefficient of variation from 0.5 to 11.1%) over the diclofenac sodium concentration range of 5.0-1000 ng/mL, with a quantification limit of 5.0 ng/mL. The method has been successfully applied to a pharmacokinetic study in which normal volunteers received 150 mg of a prototype controlled-release formulation of diclofenac sodium.

Plasma and urine concentrations of 2-(3-chloro-4[3-pyrrolinyl]phenyl) propionic acid, pirprofen, a new nonsteroidal anti-inflammatory compound, are described for normal male volunteers receiving one or more doses of the drug. Orally administered pirprofen is rapidly and almost completely absorbed from the gastrointestinal tract, resulting in maximum plasma levels in 1 to 2 hr. Mean peak levels are 23 microng/ml after an oral pirprofen dose of 200 mg; lower doses given proportionally lower levels. Administration 1 hr after a meal slightly delays the peak plasma level, but the extent of absorption is not affected significantly. Administration of pirprofen, 150 mg, 4 times daily, or 200 mg, 3 times daily, results in nearly identical plasma levels at steady-state. Pirprofen has an apparent elimination half-life of about 7 hr. The results obtained from a 200-mg pirprofen-14C dose indicate that excretion of the drug occurs primarily by the renal route in the form of metabolites and is essentially complete within 24 hr. In urine, less than 5% of the administered dose is accounted for as unchanged drug.

An automated method is described for analyzing biological samples originating from CGS 10787B drug disposition studies. The method incorporates a laboratory robot to prepare plasma and urine samples and a high performance liquid chromatographic system to simultaneously analyze for CGS 10787B, as well as metabolites and drug-related compounds (CGS 12094, CGS 17000, and CGS 17001). The robot allquots the biological sample, adds an internal standard, and performs all the steps necessary for the liquid-liquid extraction and concentration of the drug and related components, while operating unattended around the clock. Recovery and reproducibility assessments indicate good accuracy and precision for the method. The limits of detection for the method are 0.2 microgram/mL in plasma and 0.5 microgram/mL in urine, for all components.

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