Multi-Component Metabolic Classification of Commercial Feverfew Preparations via High-Field ¹H-NMR Spectroscopy and Chemometrics

Abstract

There is increasing interest in evaluating the clinical efficacy of herbal medicines. However, there are significant analytical problems associated with quality control and the measurement of the overall composition of such complex, multi-component mixtures as normally required in the pharmaceutical industry. Here we describe a novel NMR spectroscopic and pattern recognition analytical approach to investigate composition and variability of a commonly used herbal medicine. 600 MHz ¹H-NMR spectroscopy and principal components analysis (PCA) was used to discriminate between batches of 14 commercially available feverfew samples based on multi-component metabolite profiles. Two of the batches were significantly different from the other twelve. The twelve remaining classes could be classified into discrete groups by PCA on the basis of minor differences in overall chemical composition. NMR based pattern recognition (PR) analysis of extracts proved to be superior to PR analysis of HPLC traces of the same mixtures.This work indicates the potential value of NMR combined with PCA for the characterisation of complex natural product mixtures, and the discrimination of samples containing allegedly identical ingredients.

Abbreviations

PCA:principal components analysis

PC:principal component

PR:pattern recognition

TSP:3-(trimethylsilyl)-propionic-2,2,3,3-d ₄ acid, sodium salt

Feverfew - NMR spectroscopy - pattern recognition - principal components analysis - quality control - sample classification - Tanacetum parthenium - Compositae

References

• 1 Johnson E, Kadam N, Hylands D, Hylands P. Efficacy of feverfew as prophylactic treatment of migraine.  Brit Med J. 1985;  291 569-73
• 2 Awang D V, Dawson B A, Kindack D G, Crompton C W, Heptinstall S. Parthenolide content of feverfew (Tanacetum parthenium) assessed by HPLC an ¹H-NMR spectroscopy.  J Nat Prod. 1991;  54 1516-21
• 3 Awang D V, Dawson B A, Kindack D G, Crompton C W, Heptinstall S. In 30^th Annual Meeting of the ASP. San Juan, Puerto Rico; 1989
• 4 Heptinstall S, Awang D V, Dawson B A, Kindack D G, Knight D, May J. Parthenolide content and bioactivity of feverfew (Tanacetum parthenium (L.) Schultz-Bip.). Estimation of commercial and authenticated feverfew products.  J Pharm Pharmacol. 1992;  44 391-5
• 5 Jessup D, PhD. University of London 1982
• 6 Williamson E. Synergy - fact or fiction? In Herbal medicine: A concise overview for professionals. E. Ernst Butterworth-Heinemann Oxford; 2000: 43-58
• 7 Jain A K, Duin R PW, Mao J. Statistical pattern recognition: A review.  IEEE T Pattern Anal. 2000;  20 4-37
• 8 Smith R M, Burford M D. Comparison of flavonoids in feverfew varieties and related species by principal components analysis.  Chemometr Intell Lab. 1993;  18 285-91
• 9 Lazarowych N J, Pekos P. Use of fingerprinting and marker compounds for identification and standardisation of botanical drugs: Strategies for applying pharmaceutical HPLC analysis to herbal products.  Drug Inf J. 1998;  32 497-512
• 10 Knight D. Feverfew: Chemistry and biological activity.  Nat Prod Rep. 1995;  12 271-6
• 11 Williams C A, Harborne J B, Geiger H, Hoult J RS. The flavonoids of Tanacetum parthenium and T. vulgare and their anti-inflammatory properties.  Phytochemistry. 1999;  51 417-23
• 12 Nicholson J, Lindon J, Holmes E. Metabonomics: Understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data.  Xenobiotica. 1999;  29 1181-9
• 13 Holmes E, Shockcor J P. Accelerated toxicity screening using NMR and pattern recognition-based methods.  Curr Opinion Drug Disc Dev. 2000;  3 72-8
• 14 Belton P S, Colquhoun I J, Kemsley E K, Delgadillo I, Roma P, Dennis M J. Application of chemometrics to the ¹H-NMR spectra of apple juices: Discrimination between apple varieties.  Food Chem. 1998;  61 207-13
• 15 Forveille L, Vercauteren J, Rutledge D N. Multivariate statistical analysis of two dimensional NMR data to differentiate grapevine cultivars and clones.  Food Chem.. 1996;  57 441-50
• 16 Alam T M, Alam M K. Chemometric analysis of NMR spectroscopy data.  Spectroscopy. 2001;  16 18-25
• 17 El-Deredy W. Pattern recognition approaches in biomedical and clinical magnetic resonance spectroscopy: A review.  NMR Biomed. 1997;  10 99-124
• 18 Nicholson J, Foxall P J, Spraul M, Farrant R D, Lindon J. 750 MHz ¹H- and ¹H-¹³C-NMR spectroscopy of human blood plasma.  Anal Chem. 1995;  67 793-811
• 19 Brown A M, Lowe K C, Davey M R, Power J B, Knight D, Heptinstall S. Comparison of extraction procedures for parthenolide in Tanacetum parthenium .  Phytochem Anal. 1996;  7 86-91