Determination of (R)-timolol in (S)-timolol maleate active pharmaceutical ingredient: Validation of a new supercritical fluid chromatography method with an established normal phase liquid chromatography method

Add time:07/13/2019    Source:sciencedirect.com

An enantioselective supercritical fluid chromatography (SFC) method was developed and validated to meet the current European Pharmacopoeia requirements of a limit test for the determination of S-timolol maleate enantiomeric purity in timolol maleate drug substance. The developed method is presented as an alternative to the current normal phase high performance liquid chromatography (NP-HPLC) method described in the European Pharmacopoeia (Timolol Maleate Monograph). Using a 4.6 mm × 250 mm Chiralcel OD-H (dp: 5 μm) column and a mobile phase of (93:7) CO2/0.1% (v/v) TEA in MeOH delivered at 4.0 mL min−1 resolution of 2.0 was achieved within 5 min, representing a 3-fold reduction in run-time and an 11-fold reduction in solvent consumption relative to the NP-HPLC method. Method robustness was examined by the variation of flow rate (±0.5 mL min−1), column temperature (±5 °C) and column back-pressure (±10 bar) and resolution was maintained at ≥1.9 in all cases. R-timolol was resolved from all potential impurities and the limit of detection was improved by increasing the sample concentration threefold compared to the NP-HPLC method such that the method could detect the R-timolol enantiomer at 0.5% (w/w) with respect to S-timolol maleate. Additional validation parameters demonstrated that the potential of the method to be used for routine release testing of timolol maleate raw material for drug product manufacturing in which the quantitation of R-timolol impurity in S-timolol maleate drug substance would be a requirement.

We also recommend Trading Suppliers and Manufacturers of D-Timolol maleate (cas 26839-77-0). Pls Click Website Link as below: cas 26839-77-0 suppliers

Prev:Loading of vitamin E into silicone hydrogel by supercritical carbon dioxide impregnation toward controlled release of timolol maleate
Next:Gelatinized core liposomes: A new Trojan horse for the development of a novel timolol maleate glaucoma medication)