Fast and simple gas chromatographic method for simultaneous estimation of camphor, menthol and methyl salicylate in analgesic ointment: application in stability study

Abstract

A simple, rapid and sensitive gas chromatographic (GC) method with flame ionization detector (FID) has been developed and validated for simultaneous estimation of camphor, menthol and methyl salicylate (MS). Camphor, menthol and MS were separated at about 2.753, 3.206 and 3.995 min respectively on a capillary column with helium (3.3 ml/min) as carrier gas within 11 min run time. Noninterference of any peak with the peaks of interest confirms the selectivity of method. Derived quantitation limits (QL) were 0.847, 0.684 and 6.507 µg/ml for camphor, menthol and MS respectively. The linear relationship (R2 > 0.999) between analyte concentration vs detector response was established within a range of QL to 150% of label claim concentration for each analyte. Recovery of each analyte at 50, 100 and 150% of label claim concentration levels were obtained within 99.67–101.53% establishing high accuracy of the method. The method showed acceptable precision with low relative standard deviation or RSD (0.24–1.03%) between percent recoveries for each analyte. RSD for intermediate precision (inter day analysis, analyst variation) was less than 1%. The validated method was successfully applied for quantitative determination of camphor, menthol and MS in stability samples of an analgesic ointment produced by IKOP Sdn. Bhd., Malaysia.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. Braithwaite A, Smith JF (1999) Gas chromatography. In: Chromatographic methods, 5th edn. Springer, Nederland, pp 165–256

    Google Scholar 

  2. Chromatography (2014) In the United States Pharmacopoeia (USP-37), Retrieved 25 Nov, 2016, from https://hmc.usp.org/sites/default/files/documents/HMC/GCs-Pdfs/c621.pdf

  3. Fiori J, Naldi M, Gotti R (2010) HS–SPME–GC–MS for the quantitation and chiral characterization of camphor and menthol in creams. Chromatographia 72:941–947

    CAS  Article  Google Scholar 

  4. Gaudioso C, Hao J, Martin-Eauclaire MF, Gabriac M, Delmas P (2012) Menthol pain relief through cumulative inactivation of voltage-gated sodium channels. Pain 153(2):473–484

    CAS  Article  PubMed  Google Scholar 

  5. González-Peñas E, López-Alvarez M, Martínez de Narvajas F, Ursúa A (2000) Simultaneous GC determination of turpentine, camphor, menthol and methyl salicylate in a topical analgesic formulation (Dologex®). Chromatographia 52(3–4):245–248

    Article  Google Scholar 

  6. Higashi Y, Kiuchi T, Furuta K (2010) Efficacy and safety profile of a topical methyl salicylate and menthol patch in adult patients with mild to moderate muscle strain: a randomized, double-blind, parallel-group, placebo-controlled, multicenter study. Clin Ther 32(1):34–43

    CAS  Article  PubMed  Google Scholar 

  7. Hinshaw JV (2005) The flame ionization detector. Retrieved 25 Nov, 2016, from http://www.chromatographyonline.com/flame-ionization-detector

  8. ICH HARMONISED TRIPARTITE GUIDELINE STABILITY TESTING FOR NEW DOSAGE FORMS Annex to the ICH Harmonised Tripartite Guideline on Stability Testing for New Drugs and Products Q1C (1996) Retrieved 25 Nov, 2016, from http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q1C/Step4/Q1C_Guideline.pdf

  9. ICHQ2 (R1) (2005) Validation of analytical procedures: text and methodology. https://doi.org/http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf

  10. Johar P, Grover V, Topp R, Behm DG (2012) A comparison of topical menthol to ice on pain, evoked tetanic and voluntary force during delayed onset muscle soreness. Int J Sports Phys Ther 7(3):314–322

    PubMed  PubMed Central  Google Scholar 

  11. Johnston L (2013) Muscle and joint pain: topical anti-inflammatories and analgesics: therapeutic. Prof Nursing Today 17(1):4–5

    Google Scholar 

  12. Krzek J, Czekaj JS, Rzeszutko, W (2003) Validation of a method for simultaneous determination of menthol and methyl salicylate in pharmaceuticals by capillary gas chromatography with cool on-column injection. Acta Pol Pharm 60(5):343–349

    CAS  PubMed  Google Scholar 

  13. National Center for Biotechnology Information. PubChem compound database; CID = 4133. Retrieved 18 Jan, 2017 from, https://pubchem.ncbi.nlm.nih.gov/compound/4133

  14. Pauwels J, D’Autry W, Van den Bossche L, Dewever C, Forier M, Vandenwaeyenberg S et al (2012) Optimization and validation of liquid chromatography and headspace-gas chromatography based methods for the quantitative determination of capsaicinoids salicylic acid, glycol monosalicylate, methyl salicylate, ethyl salicylate, camphor and l-menthol in a topical ointment. J Pharm Biomed Anal 60: 51–58

    CAS  Article  PubMed  Google Scholar 

  15. Schreiner M (2005) Quantification of long chain polyunsaturated fatty acids by gas chromatography: evaluation of factors affecting accuracy. J Chromatogr A 1095(1–2):126–130

    CAS  Article  PubMed  Google Scholar 

  16. Scott PW (1998) Introduction to analytical gas chromatography. Marcel Dekker Inc, New York, pp 65–99

    Google Scholar 

  17. Shabir GA (2003) Validation of high-performance liquid chromatography methods for pharmaceutical analysis. J Chromatogr A 987(1–2):57–66

    CAS  Article  PubMed  Google Scholar 

  18. Shrivastava A, Gupta V, Article R (2011) Methods for the determination of limit of detection and limit of quantitation of the analytical methods. Chron Young Sci 2(1):21–25

    Article  Google Scholar 

  19. Soboleva E, Ambrus Á (2004) Application of a system suitability test for quality assurance and performance optimisation of a gas chromatographic system for pesticide residue analysis. J Chromatogr A 1027:55–65

    CAS  Article  PubMed  Google Scholar 

  20. Valdez JS, Martin DK, Mayersohn M (1999) Sensitive and selective gas chromatographic methods for the quantitation of camphor, menthol and methyl salicylate from human plasma. J Chromatogr B Biomed Sci Appl 729(1–2):163–171

    CAS  Article  PubMed  Google Scholar 

  21. Wahlich JC, Carr GP (1990) Chromatographic system suitability tests–what should we be using? J Pharm Biomed Anal 8(8–12):619–623

    CAS  Article  PubMed  Google Scholar 

  22. Wang TM, Ding LQ, Jin HJ, Shi, R, Wu JS, Zhu L et al (2015) Simultaneous quantification of multiple volatile active components in rat plasma using a headspace-solid phase dynamic extraction method coupled to gas chromatography-tandem mass spectroscopy: application in a pharmacokinetic study of Longhu Rendan pills. RSC Adv 5(38):29631–29638

    Article  Google Scholar 

  23. Yan-chao LI, Yi-xian LI, Ling-wen YAO, Zhen-guo LI (2012) GC simultaneous determination of camphor, menthol and synthetic borneol in Tongluo Qutong plaster. Chin J Pharm Anal 32(4):672–675

    Google Scholar 

  24. Zuccarini P (2010) Camphor: risks and benefits of a widely used natural product. J Appl Sci Environmen Manag 13(2):77–82

    Google Scholar 

Download references

Acknowledgements

The authors are thankful to iKOP Sdn. Bhd., Kuantan, Malaysia for providing all of the analytical laboratory facilities and the analgesic ointment sample used for this work. All authors declare that there is no conflict of interest from any aspect on this article.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Bappaditya Chatterjee.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Adib, N.A.M., Mandal, U.K., Mohamed, F. et al. Fast and simple gas chromatographic method for simultaneous estimation of camphor, menthol and methyl salicylate in analgesic ointment: application in stability study. Journal of Pharmaceutical Investigation 47, 275–285 (2017). https://doi.org/10.1007/s40005-017-0305-0

Download citation

Keywords

  • Camphor
  • Menthol
  • Methyl salicylate
  • GC-FID
  • Validation