Assay of tolnaftate and related impurities by isocratic supercritical fluid chromatography

Tolnaftate, an antifungal drug (TF) and related impurities arising from synthesis, viz., N-methyl-m-toluidine (NMmT) and beta-naphthol-1-chlorothio carbamate (beta-NCTC) can be determined by supercritical fluid chromatography. Even though it was possible to elute TF completely with neat SCF CO2, the peaks of the impurities were found to merge. The chromatographic figures of merit of the three analytes such as retention time (tR), capacity factor (k), selectivity factor (alpha), no. of theoretical plates (N), were optimized. The three compounds can be resolved in 5 min on a Hypersil (250 x 4.0 mm) 5 mu, C18 column with supercritical carbon dioxide, modified with 1.96% methanol as the mobile phase at 9.81 MPa and at 40 degrees C. Detection was carried out at 220 nm. The data as evaluated by the linear regression least squares fit method gave linearity ranges from 0.2 to 10.0 microg/mL for TF and NMmT and 0.3 to 10.0 microg/mL for beta-NCTC with correlation coefficients > 0.99. The method was successfully employed to estimate levels of 0.01% for NMmT and 0.02% for beta-NCTC with respect to TF.     

Performance comparison between packed column supercritical fluid chromatography (SFC) and HPLC using cyclandelate as the model analyte

A reproducible and fast method has been developed for the assay of cyclandelate in bulk and drug forms using packed column supercritical fluid chromatography using dicyclohexyl phthalate (DCHP) as internal standard. The drug and the internal standard were resolved by elution with supercritical fluid carbon dioxide doped with 14.29% (v/v) methanol on an RP-C₁₈ column and detected spectrophotometrically at 228 nm. Chromatographic figures of merit using C₈, C₁₈, cyano and phenyl columns have been assessed. Parallel experiments have been performed by HPLC and the data have been compared. Supercritical fluid extraction using CO₂ modified with a small amount of methanol was found to give quantitative analytical recoveries of cyclandelate from a dosage form. SFC has been shown to be a viable, faster alternative technique to HPLC generating less disposable waste.     

Assay of tolnaftate and related impurities by isocratic supercritical fluid chromatography

Tolnaftate, an antifungal drug (TF) and related impurities arising from synthesis, viz., N-methyl-m-toluidine (NMmT) and β-naphthol-1-chlorothio carbamate (β-NCTC) can be determined by supercritical fluid chromatography. Even though it was possible to elute TF completely with neat SCF CO₂, the peaks of the impurities were found to merge. The chromatographic figures of merit of the three analytes such as retention time (t_R), capacity factor (k^|), selectivity factor (α), no. of theoretical plates (N), were optimized. The three compounds can be resolved in 5 min on a Hypersil (250 × 4.0 mm) 5 μ, C₁₈ column with supercritical carbon dioxide, modified with 1.96% methanol as the mobile phase at 9.81 MPa and at 40?°C. Detection was carried out at 220 nm. The data as evaluated by the linear regression least squares fit method gave linearity ranges from 0.2 to 10.0 μg/mL for TF and NMmT and 0.3 to 10.0 μg/mL for β-NCTC with correlation coefficients > 0.99. The method was successfully employed to estimate levels of 0.01% for NMmT and 0.02% for β-NCTC with respect to TF.     

Performance comparison between packed column supercritical fluid chromatography (SFC) and HPLC using cyclandelate as the model analyte

A reproducible and fast method has been developed for the assay of cyclandelate in bulk and drug forms using packed column supercritical fluid chromatography using dicyclohexyl phthalate (DCHP) as internal standard. The drug and the internal standard were resolved by elution with supercritical fluid carbon dioxide doped with 14.29% (v/v) methanol on an RP-C₁₈ column and detected spectrophotometrically at 228 nm. Chromatographic figures of merit using C₈, C₁₈, cyano and phenyl columns have been assessed. Parallel experiments have been performed by HPLC and the data have been compared. Supercritical fluid extraction using CO₂ modified with a small amount of methanol was found to give quantitative analytical recoveries of cyclandelate from a dosage form. SFC has been shown to be a viable, faster alternative technique to HPLC generating less disposable waste. Received: 20 June 1997 / Revised: 20 October 1997 / Accepted: 26 October 1997     

Packed column supercritical fluid chromatographic separation and estimation of acetaminophen, diclofenac sodium and methocarbamol in pharmaceutical dosage forms

A reproducible and fast method has been developed for the assay of acetaminophen, methocarbamol, and diclofenac sodium in bulk and drug forms using packed column supercritical fluid chromatography employing internal standard method. The analytes were resolved by elution with supercritical fluid carbon dioxide doped with 11.1% (v/v) methanol on a Shendon-Phenyl (250x4.6 mm) 5 mum column with detection monitored spectrophotometrically at 225 nm. The densities and polarities of the mobile phase were optimised from the effects of pressure, temperature and modifier concentration on chromatograhic figures like retention time (t(R), min), retention factor (k(')) etc. Modifier concentration proved to be the most effective means for changing both retention and selectivity. Calibration data and recovery of the drug from spiked concentrations were determined to assess the viability of the method. The supercritical fluid chromatography (SFC) method was directly compared to an HPLC assay, developed in the laboratory, of the same analytes. With respect to speed and use of organic solvents SFC was found to be superior, while in all other aspects the results were similar to HPLC. The method has been successfully used for the assay of two formulations containing a combination of (A) acetaminophen and methocarbamol and (B) acetaminophen and diclofenac sodium. There was no interference from excipients. The present work validates the recent proposition that supercritical fluid chromatography using CO(2) and modifiers is a viable, faster alternative to reverse phase HPLC.