Flow Injection Analysis of Carboxylic Acid Drugs Using Cationic Dyes and On-Line Ion-Pair Extraction

Abstract

A flow injection system containing an on-line ion-pair extractor has been designed for the analysis of carboxylic acid drugs using either spectrophotometric detection with gentian violet as counterion or fluorescence detection with acridine orange. Salicylic acid, valproic acid, and ibuprofen were selected as model drugs. A mobile phase of 90:10 aqueous pH 7 phosphate buffer-absolute methanol was pumped through the system at 1 ml/min. A chloroform solution of the cationic dye was pumped into the mobile phase at 1.25 ml/min and the chloroform layer containing the dye-drug ion-pair separated prior to detection. Peak height and absorbance were linear for salicylic acid, valproic acid, and ibuprofen in the 0.5–10, 5–50, and 1–10 μg/ml ranges, respectively. Peak height and fluorescence were linear for salicylic acid, valproic acid, and ibuprofen in the 0.13–5, 2.5–50, and 0.5–20 μg/ml ranges, respectively. Accuracy and precision for the spectrophotometric assays were in the 2–6% and 3.3–6.6% ranges, respectively, and in the 0.3–4% and 1.3–5.4% ranges, respectively, for the fluorescence assays. Peak height and absorbance were also shown to be linear in the 16–500 μg/ml range for prostaglandin PGF_2α with accuracy and precision of 1–3% and 5–6%, respectively, for spiked samples. Commercial dosage forms containing valproic acid and ibuprofen were assayed by the spectrophotometric assay and found to be within acceptable USP limits. Spiked ibuprofen samples at the 5 and 10 μg/ml level were assayed using an octadecylsilane column inserted into the flow injection system. One to two percent accuracy and 2.5–5% precision were obtained for the drug using the FIA-column system.