固相萃取—反相HPLC法测定血浆中二氟尼柳的浓度

DETERMINATION OF DIFLUNISAL IN PLASMA BY RPHPLC AFTER SOLIDLIQUID EXTRACTION

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。

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 C18 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 μg·ml-1, with the lowest detection limit 002 μg·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 T1/2α and T1/2β were 140 h and 1785 h, respectively.