Skip to content
2000
Volume 21, Issue 7
  • ISSN: 1573-4110
  • E-ISSN: 1875-6727

Abstract

Purpose

Ropivacaine is a widely used local anesthetic for managing postoperative pain, particularly in procedures such as caesarean sections. While historically used as a racemate, its structural similarity to mepivacaine and bupivacaine within the pipecoloxylidide group is notable. Both enantiomers of ropivacaine exhibit similar nerve-blocking properties, but the R enantiomer is associated with increased cardiotoxicity compared to the S-Ropivacaine, like bupivacaine. This study aimed to develop and validate precise and rapid chiral chromatographic techniques for quantifying potential (R&S enantiomers).

Methods

We used normal phase chromatography with a (3,5-dimethylphenylcarbamate) immobilized-type polysaccharide stationary phase to quantify R&S enantiomers. The method followed ICH Q2(R1) guidelines, employing CHIRAL ART Amylose-SA for determining S-Ropivacaine enantiomeric purity in pharmaceutical drugs. The validation included accuracy and LOQ (limit of quantification) profiles, with measurement error assessments. Linear regression of accuracy profiles post square root transformations set acceptance limits at ±10%.

Results

The method accurately quantified R&S enantiomers, adhering to ICH Q2(R1) guidelines. Validation showed high accuracy and precise LOQ profiles. Measurement error assessments confirmed reliability. Linear regression of accuracy profiles stayed within ±10% acceptance limits, confirming the method's suitability for determining S-Ropivacaine enantiomeric purity.

Conclusion

The developed chiral chromatographic method provides an effective means of quantifying the enantiomeric purity of S-Ropivacaine in pharmaceutical drugs. Its adherence to ICH Q2(R1) guidelines ensures reliability and accuracy in measurement. This method enables precise determination of S-Ropivacaine content, which is crucial for optimizing therapeutic outcomes while minimizing the risk of cardiotoxicity associated with the R enantiomer.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cac/10.2174/0115734110321087240918112556
2024-10-04
2025-11-05

  • From This Site

    /content/journals/cac/10.2174/0115734110321087240918112556
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. AlkadiH. JbeilyR. Role of Chirality in Drugs: An Overview.Infect. Disord. Drug Targets2018182889510.2174/1871526517666170329123845 28356054
     [Google Scholar]
  2. GeorgeA.M. LiuM. Ropivacaine.StatPearls.Treasure Island, FLStatPearls Publishing2024
     [Google Scholar]
  3. EMA, United States.Available from: https://www.ema.europa.eu/en/partners-networks/international-activities/bilateral-interactions-non-eu-regulators/united-states(accessed on 31-8-2024)
  4. Francotte, E.; Lindner, W.; Mannhold, R.; Kubinyi, H.; Folkers, G., Eds.; Chirality in drug research.WeinheimWiley-VCH200610.1002/3527609431
     [Google Scholar]
  5. BrooksW.H. GuidaW.C. DanielK.G. The significance of chirality in drug design and development.Curr. Top. Med. Chem.201111776077010.2174/156802611795165098 21291399
     [Google Scholar]
  6. SanganyadoE. LuZ. FuQ. SchlenkD. GanJ. Chiral pharmaceuticals: A review on their environmental occurrence and fate processes.Water Res.201712452754210.1016/j.watres.2017.08.003 28806704
     [Google Scholar]
  7. McClureJ.H. Ropivacaine.Br. J. Anaesth.199676230030710.1093/bja/76.2.300 8777115
     [Google Scholar]
  8. CederholmI. Preliminary risk-benefit analysis of ropivacaine in labour and following surgery.Drug Saf.199716639140210.2165/00002018‑199716060‑00005 9241493
     [Google Scholar]
  9. YamashitaA. MatsumotoM. MatsumotoS. ItohM. KawaiK. SakabeT. A comparison of the neurotoxic effects on the spinal cord of tetracaine, lidocaine, bupivacaine, and ropivacaine administered intrathecally in rabbits.Anesth. Analg.200397251251910.1213/01.ANE.0000068885.78816.5B 12873946
     [Google Scholar]
  10. DeerT. KramesE.S. HassenbuschS.J. BurtonA. CarawayD. DupenS. EisenachJ. ErdekM. GrigsbyE. KimP. LevyR. McDowellG. MekhailN. PanchalS. PragerJ. RauckR. SaulinoM. SitzmanT. StaatsP. Stanton-HicksM. StearnsL. WillisK.D. WittW. FollettK. HuntoonM. LiemL. RathmellJ. WallaceM. BuchserE. CousinsM. Ver DonckA. Polyanalgesic consensus conference 2007: recommendations for the management of pain by intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel.Neuromodulation200710430032810.1111/j.1525‑1403.2007.00128.x 22150890
     [Google Scholar]
  11. Sänger-van de GriendC.E. Enantiomeric separation of alanyl and leucyl dipeptides by capillary electrophoresis with cyclodextrins as chiral selectors.Electrophoresis200021122397240410.1002/1522‑2683(20000701)21:12<2397::AID‑ELPS2397>3.0.CO;2‑F 10939451
     [Google Scholar]
  12. DossouK.S.S. ChiapP. ChankvetadzeB. ServaisA.C. FilletM. CrommenJ. Optimization of the LC enantioseparation of chiral pharmaceuticals using cellulose tris(4‐chloro‐3‐methylphenylcarbamate) as chiral selector and polar non‐aqueous mobile phases.J. Sep. Sci.201033121699170710.1002/jssc.201000049 20432231
     [Google Scholar]
  13. DossouK.S.S. ChiapP. ChankvetadzeB. ServaisA.C. FilletM. CrommenJ. Enantioresolution of basic pharmaceuticals using cellulose tris(4-chloro-3-methylphenylcarbamate) as chiral stationary phase and polar organic mobile phases.J. Chromatogr. A20091216447450745510.1016/j.chroma.2009.05.081 19552911
     [Google Scholar]
  14. HubertP. Nguyen-HuuJ.J. BoulangerB. ChapuzetE. CohenN. CompagnonP.A. DewéW. FeinbergM. LaurentieM. MercierN. MuzardG. ValatL. RozetE. Harmonization of strategies for the validation of quantitative analytical procedures.J. Pharm. Biomed. Anal.2007451829610.1016/j.jpba.2007.06.032 17716847
     [Google Scholar]
  15. HubertP. Nguyen-HuuJ.J. BoulangerB. ChapuzetE. ChiapP. CohenN. CompagnonP.A. DewéW. FeinbergM. LallierM. LaurentieM. MercierN. MuzardG. NivetC. ValatL. Harmonization of strategies for the validation of quantitative analytical procedures.J. Pharm. Biomed. Anal.200436357958610.1016/j.jpba.2004.07.027 15522533
     [Google Scholar]
  16. FDA Policy Statement for Development of New Stereoisomeric Drug.Available from: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm122883.htm(accessed on 31-8-2024)
  17. ViswanathanC.T. BansalS. BoothB. DeStefanoA.J. RoseM.J. SailstadJ. ShahV.P. SkellyJ.P. SwannP.G. WeinerR. Quantitative bioanalytical methods validation and implementation: best practices for chromatographic and ligand binding assays.Pharm. Res.200724101962197310.1007/s11095‑007‑9291‑7 17458684
     [Google Scholar]
  18. ShahV.P. MidhaK.K. FindlayJ.W.A. HillH.M. HulseJ.D. McGilverayI.J. McKayG. MillerK.J. PatnaikR.N. PowellM.L. TonelliA. ViswanathanC.T. YacobiA. Bioanalytical method validation--a revisit with a decade of progress.Pharm. Res.200017121551155710.1023/A:1007669411738 11303967
     [Google Scholar]
  19. ShahV.P. MidhaK.K. DigheS. McGilverayI.J. SkellyJ.P. YacobiA. LayloffT. ViswanathanC.T. CookC.E. McDowallR.D. Analytical methods validation: Bioavailability, bioequivalence and pharmacokinetic studies.Eur. J. Drug Metab. Pharmacokinet.199116424925510.1007/BF03189968 1823867
     [Google Scholar]
  20. ÅbergG. Toxicological and local anaesthetic effects of optically active isomers of two local anaesthetic compounds.Acta Pharmacol. Toxicol. (Copenh.)197231427328610.1111/j.1600‑0773.1972.tb00683.x 4678027
     [Google Scholar]
  21. GrafB.M. AbrahamI. EberbachN. KunstG. StoweD.F. MartinE. Differences in cardiotoxicity of bupivacaine and ropivacaine are the result of physicochemical and stereoselective properties.Anesthesiology20029661427143410.1097/00000542‑200206000‑00023 12170056
     [Google Scholar]
  22. SimonM.J. VeeringB.T. StienstraR. van KleefJ.W. BurmA.G. The effects of age on neural blockade and hemodynamic changes after epidural anesthesia with ropivacaine.Anesth. Analg.20029451325133010.1097/00000539‑200205000‑00052 11973214
     [Google Scholar]
  23. Practical guide for the management of systemic toxicity caused by local anesthetics.J. Anesth.20193311810.1007/s00540‑018‑2542‑4 30417244
     [Google Scholar]
  24. CorcoranW. ButterworthJ. WellerR.S. BeckJ.C. GerancherJ.C. HouleT.T. GrobanL. Local anesthetic-induced cardiac toxicity: A survey of contemporary practice strategies among academic anesthesiology departments.Anesth. Analg.200610351322132610.1213/01.ane.0000242515.03653.bb 17056977
     [Google Scholar]
  25. MohammedM.S. HefnawyM.M. Al-MajedA.A. AlrabiahH.K. AlgrainN.A. ObaidullahA.J. AltamimiA.S. Bin JardanY.A. Al-HossainiA.M. Development and validation of a chiral liquid chromatographic assay for enantiomeric separation and quantification of verapamil in rat plasma: Stereoselective pharmacokinetic application.Molecules2021267209110.3390/molecules26072091 33917412
     [Google Scholar]
  26. FerryN. HancockL.E. DhanjalS. Opioid Anesthesia.Updated 2023 Dec 14StatPearls.InternetTreasure Island, FLStatPearls Publishing2024
     [Google Scholar]
  27. KuthialaG. ChaudharyG. Ropivacaine: A review of its pharmacology and clinical use.Indian J. Anaesth.201155210411010.4103/0019‑5049.79875 21712863
     [Google Scholar]
  28. TejaG.S. ArchanaD. SrinuB. AliS.K.A. ReddyS.S.N. ParvezS.K. BabuP.S. SankarP.R. A Comprehensive Guide for Analytical Method Validation.Int. J. Pharm. Sci. Rev. Res.2023251710.47583/ijpsrr.2023.v82i02.002
     [Google Scholar]
  29. DhandapaniR. Playing with Selectivity for Optimal Chiral Separation.LCGC Int.20231911720
     [Google Scholar]
  30. RizzoS. BenincoriT. FontanaF. PasiniD. CirilliR. HPLC Enantioseparation of Rigid Chiral Probes with Central, Axial, Helical, and Planar Stereogenicity on an Amylose (3,5-Dimethylphenylcarbamate) Chiral Stationary Phase.Molecules20222723852710.3390/molecules27238527 36500620
     [Google Scholar]
  31. BléhautJ. FrancoP. ZhangT. LangE. ValéryE. MarcouxJ. Industrial Applications of Chiral Chromatography.Comprehensive Chirality.Elsevier201110.1016/B978‑0‑08‑095167‑6.00920‑4
     [Google Scholar]
  32. Step-by-Step Analytical Methods Validation and Protocol in the Quality System Compliance Industry.Available from:https://demarcheiso17025.com/document/Step-by-Step%20Analytical%20Methods%20Validation%20and%20Protocol%20in%20the%20Quality%20System%20Compliance%20Industry.pdf(accessed on 31-8-2024)
  33. Process Validation Guideline.2018Available from: https://www.ipa-india.org/wp-content/uploads/2023/03/forum-2018b.pdf(accessed on 31-8-2024)
  34. GrybinikS. BosakovaZ. An overview of chiral separations of pharmaceutically active substances by HPLC (2018–2020).Monatsh. Chem.202115291033104310.1007/s00706‑021‑02832‑534456367
     [Google Scholar]
  35. SangarC. Revival of capillary electrophoretic techniques in the pharmaceutical industry.LCGC North America201230954
     [Google Scholar]
  36. MasárM. Advantages and pitfalls of capillary electrophoresis of pharmaceutical compounds and their enantiomers in complex samples: Comparison of hydrodynamically opened and closed systems.Int. J. Mol. Sci.202021186852
     [Google Scholar]
  37. AhujaS. Overview of capillary electrophoresis in pharmaceutical analysis.Separat. Sci. Technol.2008918
     [Google Scholar]
  38. LiC. Analysis of repaglinide enantiomers in pharmaceutical formulations by capillary electrophoresis using 2,6-di-o-methyl-β-cyclodextrin as a chiral selector.J. Chromatog. Sci.2012508739743
     [Google Scholar]
  39. Trouble shooting capillary electrophoresis systems.Available from: https://www.promega.es/-/media/files/resources/profiles-in-dna/602/troubleshooting-capillary-electrophoresis-systems.pdf?la=en(accessed on 27-8-2024)
  40. Luque-PerezE. MazzaraM. WeberT.P. FotiN. GrazioliE. MunaroB. PinskiG. BellocchiG. Van den EedeG. SaviniC. Testing the Robustness of Validated Methods for Quantitative Detection of GMOs Across qPCR Instruments.Food Anal. Methods20136234336010.1007/s12161‑012‑9445‑z
     [Google Scholar]
  41. ShrivastavaA. GuptaV. Methods for the determination of limit of detection and limit of quantitation of the analytical methods.Chron. Young Scient.201121212510.4103/2229‑5186.79345
     [Google Scholar]
  42. ZečevićM. StankovićŽ. ŽivanovićL. JocićB. Validation of a high-performance liquid chromatographic method for the simultaneous determination of tramadol and its impurities in oral drops as a pharmaceutical formulation.J. Chromatogr. A200611191-225125610.1016/j.chroma.2005.11.105 16386751
     [Google Scholar]
  43. DeshmukhA.S. DigheP.R. MahajanV.R. KundeV.D. MhaskeG.S. AwateS.S. Comprehensive Analysis of Quality Management in Pharmaceutical Manufacturing Process.Adv. Concepts Pharmaceut. Res.20232122310.9734/bpi/acpr/v2/6663E
     [Google Scholar]
  44. GandlaK. LalithaT. HarikaR. Development and Validation of RP-HPLC Method for Simultaneous Estimation of Aceclofenac and Tramadol in Tablet Dosage Form.Asian J. Res. Pharmaceut. Sci.20155313513810.5958/2231‑5659.2015.00021.1
     [Google Scholar]
  45. HauckR.W. SchulzC. EmslanderH.P. BöhmM. Pharmacological actions of the selective and non‐selective β‐adrenoceptor antagonists celiprolol, bisoprolol and propranolol on human bronchi.Br. J. Pharmacol.199411331043104910.1111/j.1476‑5381.1994.tb17098.x 7858847
     [Google Scholar]
  46. KonishiM. HaraguchiG. KimuraS. InagakiH. KawabataM. HachiyaH. HiraoK. IsobeM. Comparative effects of carvedilol vs. bisoprolol for severe congestive heart failure.Circ. J.20107461127113410.1253/circj.CJ‑09‑0989 20354334
     [Google Scholar]
  47. PhalgunaY. NoorJ. IndrajaN. SatheeshK.G. Analytical method development and validation for the estimation of sacubitril and valsartan in combined pharmaceutical dosage forms by RP-HPLC. As.J. Res. Pharmaceut. Sci.20188191610.5958/2231‑5659.2018.00003.6
     [Google Scholar]
  48. MaliA.D. BatheR. TamboliA. Zero order and area under curve spectrophotometric methods for determination of domperidone in pharmaceutical formulation.Asian J. Pharm. Technol.20155318218710.5958/2231‑5713.2015.00026.4
     [Google Scholar]
  49. SirideviM.P. KumarH.T. RaoS.Y. RaoV.P.K. RP-HPLC Method for Quantification of Empagliflozin in Pharmaceutical Formulation.Asian J. Pharm. Technol.20199320821110.5958/2231‑5713.2019.00035.7
     [Google Scholar]
  50. LiuY. HuC.Q. Preliminary identification and quantification of residual solvents in pharmaceuticals using the parallel dual-column system.J. Chromatogr. A20071175225926610.1016/j.chroma.2007.10.042 17988671
     [Google Scholar]
  51. International council for harmonisation of technical requirements for pharmaceuticals for human use.2015Available from: https://database.ich.org/sites/default/files/ICH_Q3C-R8_Guideline_Step4_2021_0422_1.pdf(accessed on 27-8-2024)
  52. PatelA. DwivediN. KauravN. BashaniS. PatelS. SharmaH.S. Chemical analysis of pharmaceuticals: A review.J. Med. Pharmaceut. Innov.2016347
     [Google Scholar]
  53. HoushehS. Development of Rapid, Simple and Stability-Indicating Method for Determination of Azithromycin Using RP-HPLC.Asian J. Pharmaceut. Res.201772555910.5958/2231‑5691.2017.00009.0
     [Google Scholar]
  54. LodhiB. PadamwarP. PatelA. Cleaning validation for the pharmaceuticals, biopharmaceuticals, cosmetic and nutraceuticals industries.J. Innov. Pharm. Biol. Sci.2004112738
     [Google Scholar]
  55. AneesA. BahazeqA.A. RehmanM-U. AkbarS. MehveenJ. JuveriaM. Development and Validation of Memantine Hydrochloride by RP-HPLC Method.Asian J. Pharmaceut. Res.201992697410.5958/2231‑5691.2019.00011.X
     [Google Scholar]
  56. AmbadekarS.R. IyerB.K. LokhandeM.V. Validation of Pharmaceutical (API) Bulk Drug by HPLC Methods.J. Appl. Chem.2018112120
     [Google Scholar]
  57. Stability testing:photostability testing of new drug substances and products Q1B.1996Available from: https://database.ich.org/sites/default/files/Q1B%20Guideline.pdf(accessed on 27-8-2024)
  58. MauryaC.P. LokhandeM.V. Characterization and validation of impurities related to pharmaceutical bulk drug (API) by using some analytical techniques.Int. J. Pharm. Sci. Res.20178833253340
     [Google Scholar]
/content/journals/cac/10.2174/0115734110321087240918112556
Loading
Novel Chiral HPLC Method for Accurate Identification and Quantification of R&S Enantiomers in Ropivacaine on Immobilized Chiral Stationary Phase: Development and Validation
Current Analytical Chemistry 21, 816 (2025); https://doi.org/10.2174/0115734110321087240918112556
/content/journals/cac/10.2174/0115734110321087240918112556
/content/journals/cac/10.2174/0115734110321087240918112556
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): cardiotoxicity; chiral chromatography; enantiomeric purity; method validation; R&S enantiomers; Ropivacaine

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test