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

Marley, Adrian and Connolly, Damian (2014) 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. Journal of Chromatography A, 1325. pp. 213-220. ISSN 0021-9673

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Abstract

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 4.6mm×250mm Chiralcel OD-H (dp: 5μm) column and a mobile phase of (93:7) CO2/0.1% (v/v) TEA in MeOH delivered at 4.0mLmin-1 resolution of 2.0 was achieved within 5min, 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 (±0.5mLmin-1), column temperature (±5°C) and column back-pressure (±10bar) 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.

Item Type:	Article
Additional Information:	Funding Information: The authors wish to thank the management of Allergan Pharmaceuticals Ireland Ltd. for supporting this work. Invaluable technical assistance from Mr. Stephen Fuller is greatly appreciated. The authors also acknowledge Science Foundation Ireland for funding under the Strategic Research Cluster Programme (Grant Number 08/SRC/B1412 ) and Mr. Declan Murray of Agilent Technologies Ireland for provision of the SFC instrumentation.
Uncontrolled Keywords:	/dk/atira/pure/subjectarea/asjc/1600/1602
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Depositing User:	Admin SSL
Date Deposited:	19 Oct 2022 23:03
Last Modified:	22 Jun 2023 16:05
URI:	http://repository-testing.wit.ie/id/eprint/3790

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