Fourier Transform Ion Cyclotron Resonance Mass Spectrometry for the Characterisation of Kavalactones in the Kava Plant: Elemental Formulae Confirmation by Dual Spray Accurate Mass Measurement and Structural Confirmation by Infrared Multiphoton Dissociation and Sustained Off-Resonance Irradiation Collision Induced Dissociation
Restricted accessResearch articleFirst published online August, 2006
Fourier Transform Ion Cyclotron Resonance Mass Spectrometry for the Characterisation of Kavalactones in the Kava Plant: Elemental Formulae Confirmation by Dual Spray Accurate Mass Measurement and Structural Confirmation by Infrared Multiphoton Dissociation and Sustained Off-Resonance Irradiation Collision Induced Dissociation
Roots and extracts of the kava plant have been used in herbal medicine to treat sleep disturbances, stress and anxiety, although reported cases of liver toxicity led to many countries restricting its sale. The detection of the presence of kava in many medicinal products requires the use of methods capable of identifying the kavalactones with high certainty. Here, we describe the use of Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) for the characterisation of six kavalactones (kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin and desmethoxyyangonin) utilising accurate mass measurement for the determination of their elemental formulae and product ion MS [both sustained off-resonance irradiation collision-induced dissociation and infrared multiphoton dissociation (SORI-CID and IRMPD)] for structural confirmation. High performance liquid chromatography/FT-ICR-MS with a dual spray system for internal calibration of mass spectra was employed for accurate mass measurement and the determination of elemental formulae of the kavalactones in both standards and a root extract to confirm the presence of the kavalactones in the root powder. Mass accuracy of < 1 ppm was achieved. For structural confirmation, the IRMPD and SORI-CID spectra of the kavalactones in standards and a kava root powder extract were compared. Accurate mass measurement of the product ions was also conducted by external calibration and the elemental formula determined to aid with structural confirmation. The presence of the same fragment ions detected in the standards as in the extract further confirmed the presence of the kavalactones in the kava root powder with high certainty.
van WykB. and WinkM., Medicinal Plants of the World.Briza Publications, Pretoria, South Africa, p. 243 (2004).
2.
SteinerG.G., “The Correlation between Cancer Incidence and Kava Consumption”, Hawaii Med. J.59, 420 (2000).
3.
BiliaA.R.ScaliseL.BergonziM.C. and VincieriF.F., “Analysis of Kavalactones from Piper Methysticum (kava-kava)”, J. Chromatogr. B812, 203 (2004).
4.
DragullK.YoshidaW.Y. and TangC., “Piperidine Alkaloids from Piper Methysticum”, Phytochemistry63, 193 (2003). doi: 10.1016/S0031-9422(03)00111-0
5.
SinghY.N. (Ed.), Kava: From Ethnology to Pharmacology.CRC Press, Boca Raton, Florida, USA, p. 76 (2004).
6.
SinghY.N. (Ed.), Kava: From Ethnology to Pharmacology.CRC Press, Boca Raton, Florida, USA, p. 23 (2004).
7.
HeX.LinL.Z. and LianL.Z., “Electrospray High Performance Liquid Chromatography-Mass Spectrometry in Phytochemical Analysis of Kava (piper Methysticum) Extract”, Planta Medic.63, 70 (1997).
8.
BobeldijkI.BoonzaaijerG.Spies-FaberE.J. and VaesW.H.J., “Determination of Kava Lactones in Food Supplements by Liquid Chromatography-Atmospheric Pressure Chemical Ionisation Tandem Mass Spectrometry”, J. Chromatogr. A1067, 107 (2005). doi: 10.1016/j.chroma.2005.01.013
9.
WhittonP.A.LauA.SalisburyA.WhitehouseJ. and EvansC.S., “Kava Lactones and the Kava-Kava Controversy”, Phytochemistry64, 673 (2003). doi: 10.1016/S0031-9422(03)00381-9
10.
LoewD. and FranzG., “Quality Aspects of Traditional and Industrial Kava-Extracts”, Phytomedicine10, 610 (2003). doi: 10.1078/094471103322331638
11.
SmithR.M.ThakrarH.ArowoloT.A. and ShafiA.A., “High Performance Liquid Chromatography of Kava Lactones from Piper Methysticum”, J. Chromatrogr.283, 202 (1984).
12.
ChengD.LigardA.O.DuffieldP.H.DuffieldA.M. and BrophyJ.J., “Identification by Methane Chemical Ionization Gas Chromatography/Mass Spectrometry of the Products Obtained by Steam Distillation and Aqueous Acid Extraction of Commercial Piper Methysticum”, Biomed. Environ. Mass Spectrom.17, 371 (1988). doi: 10.1002/bms.1200170505
13.
DuffieldA.M. and LidgardR.O., “Analysis of Kava Resin by Gas Chromatography and Electron Impact and Methane Negative Ion Chemical Ionisation Mass Spectrometry. New Trace Constituents of Kava Resin”, Biomed Mass Spectrom.13, 621 (1986). doi: 10.1002/bms.1200131107
14.
ShaoY.HeK.ZhengB. and ZhengQ., “Reversed-phase High Performance Liquid Chromatographic Method for Quantitative Analysis of the Six Major Kavalactones in Piper Methysticum”, J. Chromatogr. A825, 1 (1998). doi: 10.1016/S0021-9673(98)00699-2
15.
GaubM.BrockeA.RoosG. and KovarK.A., “High Performance Liquid Chromatography-Coordination Ion Spray-Mass Spectrometry (HPLC-CIS/MS): A New Tool for the Analysis of Non-polar Compound Classes in Plants Extracts Using the Example of Piper Methysticum Forst”, Phytochem. Anal.15, 300 (2004). doi: 10.1002/pca.782
16.
TarbahF.MahlerH.KardelB.WeinmannW.HafnerD. and DaldrupTh., “Kinetics of Kavain and its Metabolites after Oral Application”, J. Chromatogr. B789, 115 (2003).
17.
Council Directive 96/23/EC of 29th April 1996, “Measures to Monitor Certain Substances and Residues therof in Live Animals and Animal Products”, Official Journal of the European Communities, L221/8 (1996).
18.
FDA Guidance for Industry, “Mass Spectrometry for Confirmation of the Identity of Animal Drug Residues”, (2003).
19.
WebbK.“Optimisation of the Number of Ions which are Acceptable for Identifying Difference Chemical Species Using LC-MS, An Evaluation of Quantitation and Identification,” Report LGC/VAM/1998/071, (1998).
20.
BristowA.W.T.“Accurate Mass Measurement for the Determination of Elemental Formula – A Tutorial”, Mass Spectrom. Rev.25(1), 99 (2005). doi: 10.1002/mas.20058
21.
MarshallA.G., “Scaling MS Plateaus with High-Resolution FT-ICRMS”, Anal. Chem.74, 253A (2002). doi: 10.1021/ac015584h
22.
MarshallA.G.HendricksonC.L. and JacksonG.S., “Fourier Transform Ion Cyclotron Resonance Mass Spectrometry: A Primer”, Mass Spectrom. Rev.17, 1 (1998). doi: 10.1002/(SICI)1098-2787(1998)17:1<1::AID-MAS1>3.0.CO;2-K
23.
HugheyC.A.HendricksonC.L.RodgersR.P. and MarshallA.G., “Elemental Composition Analysis of Processed and Unprocessed Diesel Fuel by Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry”, Energy and Fuels15, 1186 (2001). doi: 10.1021/ef010028b
24.
NepomucenoA.I.MuddimanD.C.BergenH.R.CraigheadJ.R.BurkeM.J.CaskeyP.E. and AllanJ.A., “Electrospray Ionization Source for Confident Generation of Accurate Mass Tags Using Liquid Chromatography Fourier Transform Ion Cyclotron Resonance Mass Spectrometry”, Anal. Chem.75, 3079 (2003). doi: 10.1021/ac0342471
25.
SmithR.D.AndersonG.A.LiptonM.S.LjiljanaP.ShenY.ConradsT.P.VeenstraT.D. and UdsetH.R., “An accurate mass tag strategy for quantitative and high-throughput proteome measurements”, Proteomics2, 513 (2002). doi: 10.1002/1615-9861(200205)2:5<513::AID-PROT513>3.0.CO;2-W
26.
BuschK.L.GlishG.L. and McLuckeyS.A., Mass Spectrometry Mass Spectrometry: Techniques and Applications of Tandem Mass Spectrometry.VCH Publishers, Weinheim, Germany (1988).
27.
WoodinR.L.BomseD.S. and BeauchampJ.L., “Multiphoton Dissociation of Molecules with Low Power Continuous Wave Infrared Laser Radiation”, J. Am. Chem. Soc.100, 3248 (1978). doi: 10.1021/ja00478a065
28.
TonnerD.S. and McMahonT.B., “Consecutive Infrared Multiphoton Dissociations in a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer”, Anal. Chem.69, 4735 (1997). doi: 10.1021/ac970727e
29.
HofstadlerS.A.GriffeyR.H.LjiljanaP. and SmithR.D., “The Use of a Stable Internal Mass Standard for Accurate Mass Measurements of Oligonucleotide Fragment Ions using Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry with Infrared Multiphoton Dissociation”, Rapid Commun. Mass Spectrom.12, 1400 (1998). doi: 10.1002/(SICI)1097-0231(19981015)12:19<1400::AID-RCM337>3.0.CO;2-T
30.
HofstadlerS.A.Sannes-LoweryK.A. and GriffeyR.H., “m/z-Selective Infrared Multiphoton Dissociation in a Penning Trap using Sidekick Trapping and an rf-Tickle Pulse”, Rapid Commun. Mass Spectrom.15, 945 (2001). doi: 10.1002/rcm.312
31.
FukuiK.NaitoY.AkiyamaY. and TakahashiK., “Fragmentation Study of Peptides using Fourier Transform Ion Cyclotron Resonance with Infrared Multiphoton Dissociation: Experiment and Simulation”, Eur. J. Mass Spectrom.10, 639 (2004). doi: 10.1255/ejms.656
32.
KosakaT.Yoneyama-TakazawaT.KubotaK.MatsuokaT.SatoI.SasakiT. and TanakaY., “Protein Identification by Peptide Mass Fingerprinting and Peptide Sequence Tagging with Alternating Scans of Nano-Liquid Chromatography/Infrared Multiphoton Dissociation Fourier Transform Ion Cyclotron Resonance Mass Spectrometry”, J. Mass Spectrom.38, 1281 (2003). doi: 10.1002/jms.545
33.
EmmettM.R., “Determination of Post-Translational Modifications of Proteins by High-Sensitivity, High-Resolution Fourier Transform Ion Cyclotron Resonance Mass Spectrometry”, J. Chromatrogr. A1013, 203 (2003).
34.
ZhangJ.SchubotheK.LiB.RussellS. and LebrillaC.B., “Infrared Multiphoton Dissociation of O-Linked Mucin-Type Oligosaccharides”, Anal. Chem.77, 208 (2005). doi: 10.1021/ac0489824
35.
GoolsbyB.J. and BrodbeltJ.S., “Tandem Infrared Multiphoton Dissociation and Collisionally Activated Dissociation Techniques in a Quadrupole Ion Trap”, Anal. Chem.73, 1270 (2001). doi: 10.1021/ac001161o
36.
CaravattiP. and AllemannM., “The ‘Infinity’ Cell: A New Trapped Ion Cell with Radiofrequency Covered Trapping Electrodes for Fourier Transform Ion Cyclotron Resonance Mass Spectrometry”, Org. Mass Spectrom.26, 514 (1991). doi: 10.1002/oms.1210260527
37.
HernimanJ.M.BristowA.W.T.O'ConnorG.JarvisJ. and LangleyG.J., “Improved Precision and Accuracy for High-Performance Liquid Chromatography/FourierTransform Ion Cyclotron Resonance Mass Spectrometric Exact Mass Measurement of Small Molecules from the Simultaneous and Controlled Introduction of Internal Calibrants via a Second Electrospray Nebuliser”, Rapid Commun. Mass Spectrom.18, 3035 (2004). doi: 10.1002/rcm.1729
