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Determination of Menthol in Plasma and Urine by Gas Chromatography/Mass Spectrometry (GC/MS)

  • Judy Peat
  • Clint Frazee
  • Gregory Kearns
  • Uttam GargEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1383)

Abstract

Menthol, a monoterpene, is a principal component of peppermint oil and is used extensively in consumer products as a flavoring aid. It is also commonly used medicinally as a topical skin coolant; to treat inflammation of the mucous membranes, digestive problems, and irritable bowel syndrome (IBS); and in preventing spasms during endoscopy and for its spasmolytic effect on the smooth muscle of the gastrointestinal tract. Menthol has a half life of 3–6 h and is rapidly metabolized to menthol glucuronide which is detectable in urine and serum following menthol use. We describe a method for the determination of total menthol in human plasma and urine using liquid/liquid extraction, gas chromatography/mass spectrometry (GC/MS) in selected ion monitoring mode and menthol-d4 as the internal standard. Controls are prepared with menthol glucuronide and all samples undergo enzymatic hydrolysis for the quantification of total menthol. The method has a linear range of 5–1000 ng/mL, and coefficient of variation <10 %.

Key words

Menthol GCMS Peppermint oil Irritable bowel syndrome 

References

  1. 1.
    Liu B, Fan L, Balakrishna S, Sui A, Morris JB, Jordt SE (2013) TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. Pain 154:2169–2177PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Farco JA, Grundmann O (2013) Menthol—pharmacology of an important naturally medicinal “cool”. Mini Rev Med Chem 13:124–131CrossRefPubMedGoogle Scholar
  3. 3.
    Kamatou GP, Vermaak I, Viljoen AM, Lawrence BM (2013) Menthol: a simple monoterpene with remarkable biological properties. Phytochemistry 96:15–25CrossRefPubMedGoogle Scholar
  4. 4.
    Pittler MH, Ernst E (1998) Peppermint oil for irritable bowel syndrome: a critical review and metaanalysis. Am J Gastroenterol 93:1131–1135CrossRefPubMedGoogle Scholar
  5. 5.
    Ford AC, Talley NJ, Spiegel BM, Foxx-Orenstein AE, Schiller L, Quigley EM, Moayyedi P (2008) Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. BMJ 337:a2313PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Rozza AL, Hiruma-Lima CA, Takahira RK, Padovani CR, Pellizzon CH (2013) Effect of menthol in experimentally induced ulcers: pathways of gastroprotection. Chem Biol Interact 206:272–278CrossRefPubMedGoogle Scholar
  7. 7.
    Gelal A, Jacob P 3rd, Yu L, Benowitz NL (1999) Disposition kinetics and effects of menthol. Clin Pharmacol Ther 66:128–135CrossRefPubMedGoogle Scholar
  8. 8.
    Mascher H, Kikuta C, Schiel H (2001) Pharmacokinetics of menthol and carvone after administration of an enteric coated formulation containing peppermint oil and caraway oil. Arzneimittelforschung 51:465–469PubMedGoogle Scholar
  9. 9.
    Hamasaki K, Kato K, Watanabe T, Yoshimura Y, Nakazawa H, Yamamoto A, Matsunaga A (1998) Determination of l-menthol in pharmaceutical products by high performance liquid chromatography with polarized photometric detection. J Pharm Biomed Anal 16:1275–1280CrossRefPubMedGoogle Scholar
  10. 10.
    Kaffenberger RM, Doyle MJ (1990) Determination of menthol and menthol glucuronide in human urine by gas chromatography using an enzyme-sensitive internal standard and flame ionization detection. J Chromatogr 527:59–66CrossRefPubMedGoogle Scholar
  11. 11.
    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 60:343–349PubMedGoogle Scholar
  12. 12.
    Pauwels J, D’Autry W, Van den Bossche L, Dewever C, Forier M, Vandenwaeyenberg S, Wolfs K, Hoogmartens J, Van Schepdael A, Adams E (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 formulation. J Pharm Biomed Anal 60:51–58CrossRefPubMedGoogle Scholar
  13. 13.
    Schulz K, Bertau M, Schlenz K, Malt S, Dressler J, Lachenmeier DW (2009) Headspace solid-phase microextraction-gas chromatography-mass spectrometry determination of the characteristic flavourings menthone, isomenthone, neomenthol and menthol in serum samples with and without enzymatic cleavage to validate post-offence alcohol drinking claims. Anal Chim Acta 646:128–140CrossRefPubMedGoogle Scholar
  14. 14.
    Spichiger M, Muhlbauer RC, Brenneisen R (2004) Determination of menthol in plasma and urine of rats and humans by headspace solid phase microextraction and gas chromatography—mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 799:111–117CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Judy Peat
    • 1
  • Clint Frazee
    • 1
  • Gregory Kearns
    • 1
    • 2
  • Uttam Garg
    • 1
    Email author
  1. 1.Department of Pathology and Laboratory MedicineChildren’s Mercy Hospitals and ClinicsKansas CityUSA
  2. 2.Department of PediatricsChildren’s Mercy Hospitals and ClinicsKansas CityUSA

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