Development and validation of a LC method for the enantiomeric purity determination of S-ropivacaine in a pharmaceutical formulation using a recently commercialized cellulose-based chiral stationary phase and polar non-aqueous mobile phase.
[en] Ropivacaine is the first enantiomerically pure long-acting local anaesthetic used for surgical anaesthesia and post-operative pain relief. A liquid chromatographic (LC) method using acetonitrile as the main solvent and cellulose tris(4-chloro-3-methylphenylcarbamate) coated on silica as chiral stationary phase was successfully developed and applied for the enantiomeric purity determination of S-ropivacaine in a pharmaceutical formulation (Naropin((R))). The key role played by the acidic additive (trifluoroacetic acid or formic acid) in the enantioseparation of basic drugs in these LC systems was demonstrated by the reversal of ropivacaine enantiomers elution order observed when both acids were compared. In order to elute the enantiomeric impurity (R-ropivacaine) before S-ropivacaine, formic acid (FA) was selected. The temperature and the percentages of acidic additive and hexane in the mobile phase were found to significantly influence the retention and resolution of these enantiomers. The optimized mobile phase consisted of ACN/0.1% DEA/0.2% FA/5% hexane (v/v/v/v). The temperature was set at 35 degrees C to avoid the interference from a peak system related to the presence of water in the sample on ropivacaine enantiomers. The LC method was then fully validated applying the strategy based on total measurement error and accuracy profiles. The accuracy profile obtained by linear regression after square root transformation was selected, the acceptance limits being settled at +/-10% for the intended use of this analytical method. The relative bias was lower than 1.5%, while the RSD values for repeatability and intermediate precision were both below 1.0%. The limit of detection (LOD) and the limit of quantification (LOQ) were found to be about 0.2 and 1.0 mug/mL, respectively, corresponding to 0.02 and 0.1% of the enantiomeric impurity in S-ropivacaine.
Research Center/Unit :
CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège
CHIAP, Patrice ; Centre Hospitalier Universitaire de Liège - CHU > Pharmacologie clinique
Servais, Anne-Catherine ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments
Fillet, Marianne ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments
Crommen, Jacques ; Université de Liège - ULiège > Département de pharmacie > Département de pharmacie
Language :
English
Title :
Development and validation of a LC method for the enantiomeric purity determination of S-ropivacaine in a pharmaceutical formulation using a recently commercialized cellulose-based chiral stationary phase and polar non-aqueous mobile phase.
Publication date :
2011
Journal title :
Journal of Pharmaceutical and Biomedical Analysis
ISSN :
0731-7085
eISSN :
1873-264X
Publisher :
Elsevier, Amsterdam, Netherlands
Volume :
54
Issue :
4
Pages :
687-93
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique BELSPO - SPP Politique scientifique - Service Public Fédéral de Programmation Politique scientifique
Commentary :
Copyright (c) 2010 Elsevier B.V. All rights reserved.
FDA Policy Statement for Development of New Stereoisomeric Drug, (accessed 20.05.10). http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm122883.htm.
Francotte E., Lindner W. Chirality in Drug Research 2006, Wiley-VCH, Weinheim.
Markham A., Faulds D. Ropivacaine: a review of its pharmacology and therapeutic use in regional anaesthetisia. Drugs 1996, 52:429-449.
Aberg G., Dhuner K.G., Sydnes G. Studies on the duration of local anaesthesia: structure/activity relationships in a series of homologous local anaesthetics. Acta Pharmacol. Toxicol. 1977, 41:432-434.
Akerman B., Hellberg I.B., Trossvik C. Primary evaluation of the local anaesthetic properties of amino amide agent ropivacaine (LEA 103). Acta Anaesthesiol. Scand. 1988, 32:571-578.
Mcclure J.M., Ropivacaine Br. J. Anaesth. 1996, 76:300-307.
Sänger-van de Griend C.E., Gröningsson K. Validation of a capillary electrophoresis method for the enantiomeric purity testing of ropivacaine, a new local anaesthetic compound. J. Pharm. Biomed. Anal. 1996, 14:295-304.
Sänger-van de Griend C.E., Wahlström H., Gröningsson K., Widahl-Näsman M. A chiral capillary ellectrophoresis method for ropivacaine hydrochloride in pharmacutical formulations: validation and comparison with chiral liquid chromatography. J. Pharm. Biomed. Anal. 1997, 15:1051-1061.
Dossou K.S.S., Chiap P., Chankvetadze B., Servais A.-C., Fillet M., Crommen J. Enantioresolution of basic pharmaceuticals using cellulose tris(4-chloro-3 methylphenylcarbamate) as chiral stationary phase and polar organic mobile phases. J. Chromatogr. A 2009, 1216:7450-7455.
Dossou K.S.S., Chiap P., Chankvetadze B., Servais A.-C., Fillet M., Crommen J. Optimization of the LC enantioseparation of chiral pharmaceuticals using cellulose tris(4-chloro-3-methylphenylcarbamate) as chiralselector and polar non-aqueous mobile Phases. J. Sep. Sci. 2010, 33:1699-1707.
Hubert Ph., Nguyen-Huu J.-J., Boulanger B., Chapuzet E., Chiap P., Cohen N., Compagnon P.-A., Dewe W., Feinberg M., Lallier M., Laurentie M., Mercier N., Muzard G., Nivet C., Valat L. Validation of quantitative analytical procedure: harmonization of approaches. STP Pharma Pratiques 2003, 13:101-138.
Wozniak T.J., Bopp R.J., Jensen E.C. Chiral drugs: an industrial analytical perspective. J. Pharm. Biom. Anal. 1991, 9:363-382.
Cirilli R., Ferretti R., Gallinella B., Zanitti L., La Torre F. A new application of stopped-flow chiral HPLC: inversion of enantiomer elution order. J. Chromatogr. A 2004, 1061:27-34.
Hubert Ph., Nguyen-Huu J.-J., Boulanger B., Chapuzet E., Chiap P., Cohen N., Compagnon P.-A., Dewe W., Feinberg M., Lallier M., Laurentie M., Mercier N., Muzard G., Nivet C., Valat L. Harmonization of strategies for the validation of quantitative analytical procedures: a SFSTP proposal - part I. J. Pharm. Biomed. Anal. 2004, 36:579-586.
Hubert Ph., Nguyen-Huu J.-J., Boulanger B., Chapuzet E., Chiap P., Cohen N., Compagnon P.-A., Dewe W., Feinberg M., Lallier M., Laurentie M., Mercier N., Muzard G., Nivet C., Valat L. Quantitative analytical procedures: Harmonization of the appraoches - Part II. STP Pharma Pratiques 2006, 16:30-60.
Viswanathan C.T., Bansal S., Booth B., DeStefano A.J., Rose M.J., Sailstad J., Shah V.P., Skelly J.P., Swann P.G., Weiner R. Workshop/conference report - quantitative bioanalytical methods validation and implementation: Best practices for chromatographic and ligand binding assays. AASP J. 2007, 9:E30-E42.
Shah V.P., Midha K.K., Dighe S., McGilveray I.J., Skelly J.P., Jacobi A., Layloff T., Viswanathan C.T., Cook C.E., McDowall R.D., Pittman K.A., Spector S. Analytical methods validation: biovailability, bioequivalence and pharmacokinetic studies. J. Pharm. Sci. 1992, 81:309-312.
Shah V.P., Midha K.K., Findlay J.W.A., Hill H.M., Hulse J.D., McGilveray I.J., McKay G., Miller K.J., Patnaik R.N., Powell M.I., Tonelli A., Viswanathan C.T., Jacobi A. Bioanalytical method validation - a revisit with a decade of progress. Pharm. Res. 2000, 17:1551-1557.
