[Determination of diflunisal in plasma by RP-HPLC after solid-liquid extraction]

A RP-HPLC method was developed with solid-liquid extraction technique. Plasma sample was extracted on a macroreticular resin cartridge with methanol--glacial acetic acid (99:1) as elution solvent. After extraction, the assay was carried out on a Spherisorb C18 column with p-phenylphenol as internal standard. The mobile phase is a mixture of methanol--water--glacial acetic acid (66:30:4). UV detection was performed at 250 nm. The flow rate was 1.0 ml.min-1. A good linearity was found at the concentration range from 0.5 to 100 micrograms.ml-1, with the lowest detection limit 0.02 microgram.ml-1 (S/N = 2). The extraction and method recoveries were 91.65% and 97.25% respectively, while the RSD for the within-day and between-day precision were all less than 10%. The above method was applied to determine the plasma concentration of difunisal in three human volunteers after a single oral dosage of 300 mg. Two hours after administration, the plasma concentration of diflunisal reached maximum level. A two compartment method was used to study the pharmacokinetic parameters. The T1/2 alpha and T1/2 beta were 1.40 h and 17.85 h, respectively.