固相萃取—反相HPLC法测定血浆中二氟尼柳的浓度

采用固相萃取方法,以大孔网格树脂小柱净化样本,建立了快速、灵敏的反相HPLC法。方法在0.5～100μg·ml^-1浓度范围内线性关系良好,最低检出限0.02μg·ml^-1(S/N=2),萃取回收率和方法回收率分别为91.65%及97.25%,日内、日间精密度均小于10%。用此方法测定了人血浆中二氟尼柳的浓度,并对单剂量口服给药后的药代动力学作了初步探讨。

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.