Quantification of Silymarin in Silybi mariani fructus: Challenging the Analytical Performance of Benchtop vs. Handheld NIR Spectrometers on Whole Seeds

Sophia Mayr; Simon Strasser; Christian G. Kirchler; Florian Meischl; Stefan Stuppner; Krzysztof B. Beć; Justyna Grabska; Sonja Sturm; Hermann Stuppner; Michael A. Popp; Günther K. Bonn; Christian W. Huck

doi:10.1055/a-1326-2497

Planta Medica, Table of Contents

Planta Med 2022; 88(01): 20-32
DOI: 10.1055/a-1326-2497

Natural Product Chemistry and Analytical Studies

Original Papers

Quantification of Silymarin in Silybi mariani fructus: Challenging the Analytical Performance of Benchtop vs. Handheld NIR Spectrometers on Whole Seeds

Sophia Mayr‡

¹Institute of Analytical Chemistry and Radiochemistry, University of Innsbruck, Innsbruck, Austria

,

Simon Strasser‡

¹Institute of Analytical Chemistry and Radiochemistry, University of Innsbruck, Innsbruck, Austria

,

Christian G. Kirchler

¹Institute of Analytical Chemistry and Radiochemistry, University of Innsbruck, Innsbruck, Austria

,

Florian Meischl

¹Institute of Analytical Chemistry and Radiochemistry, University of Innsbruck, Innsbruck, Austria

,

Stefan Stuppner

¹Institute of Analytical Chemistry and Radiochemistry, University of Innsbruck, Innsbruck, Austria

²ADSI – Austrian Drug Screening Institute, Innsbruck, Austria

,

Krzysztof B. Beć

¹Institute of Analytical Chemistry and Radiochemistry, University of Innsbruck, Innsbruck, Austria

,

Justyna Grabska

¹Institute of Analytical Chemistry and Radiochemistry, University of Innsbruck, Innsbruck, Austria

,

Sonja Sturm

³Institute of Pharmacognosy, University of Innsbruck, Innsbruck, Austria

,

Hermann Stuppner

³Institute of Pharmacognosy, University of Innsbruck, Innsbruck, Austria

,

Michael A. Popp

⁴Michael Popp Research Institute of New Phyto Entities, University of Innsbruck, Innsbruck, Austria

,

Günther K. Bonn

¹Institute of Analytical Chemistry and Radiochemistry, University of Innsbruck, Innsbruck, Austria

²ADSI – Austrian Drug Screening Institute, Innsbruck, Austria

,

Christian W. Huck

¹Institute of Analytical Chemistry and Radiochemistry, University of Innsbruck, Innsbruck, Austria

› Author Affiliations

Abstract

The content of the flavonolignan mixture silymarin and its individual components (silichristin, silidianin, silibinin A, silibinin B, isosilibinin A, and isosilibinin B) in whole and milled milk thistle seeds (Silybi mariani fructus) was analyzed with near-infrared spectroscopy. The analytical performance of one benchtop and two handheld near-infrared spectrometers was compared. Reference analysis was performed with HPLC following a Soxhlet extraction (European Pharmacopoeia) and a more resource-efficient ultrasonic extraction. The reliability of near-infrared spectral analysis determined through partial least squares regression models constructed independently for the spectral datasets obtained by the three spectrometers was as follows. The benchtop device NIRFlex N-500 performed the best both for milled and whole seeds with a root mean square error of CV between 0.01 and 0.17%. The handheld spectrometer MicroNIR 2200 as well as the microPHAZIR provided a similar performance (root mean square error of CV between 0.01 and 0.18% and between 0.01 and 0.23%, respectively). We carried out quantum chemical simulation of near-infrared spectra of silichristin, silidianin, silibinin, and isosilibinin for interpretation of the results of spectral analysis. This provided understanding of the absorption regions meaningful for the calibration. Further, it helped to better separate how the chemical and physical properties of the samples affect the analysis. While the study demonstrated that milling of samples slightly improves the performance, it was deemed to be critical only for the analysis carried out with the microPHAZIR. This study evidenced that rapid and nondestructive quantification of silymarin and individual flavonolignans is possible with miniaturized near-infrared spectroscopy in whole milk thistle seeds.

Key words

NIR - handheld spectrometer - silymarin - Silybi mariani fructus - Silybum marianum - Asteraceae

Full Text

References

References
1 Rady MR. Plant biotechnology and medicinal plants periwinkle, milk thistle and foxglove. Cham, Switzerland: Springer Nature; 2019
2 Abenavoli L, Izzo AA, Milić N, Cicala C, Santini A, Capasso R. Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. Phyther Res 2018; 32: 2202-2213
3 Flora K, Hahn M, Rosen H, Benner K. Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol 1998; 93: 139-143
4 Albassam AA, Frye RF, Markowitz JS. The effect of milk thistle (Silybum marianum) and its main flavonolignans on CYP2C8 enzyme activity in human liver microsomes. Chem Biol Interact 2017; 271: 24-29
5 Alhidary IA, Rehman Z, Khan RU, Tahir M. Anti-aflatoxin activities of milk thistle (Silybum marianum) in broiler. Worlds Poult Sci J 2017; 73: 559-566
6 Campos R, Garrido A, Guerra R, Valenzuela A. Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta Med 1989; 55: 417-419
7 Kwon D, Jung Y, Kim S, Kim Y, Choi D, Kim Y. Alterations in sulfur amino acid metabolism in mice treated with silymarin: a novel mechanism of its action involved in enhancement of the antioxidant defense in liver. Planta Med 2013; 79: 997-1002
8 Kirchler CG, Pezzei CK, Be B, Mayr S, Ishigaki M, Ozaki Y, Huck CW. Critical evaluation of spectral information of benchtop vs. portable near-infrared spectrometers: quantum chemistry and two- dimensional correlation spectroscopy for a better understanding of PLS regression models of the rosmarinic acid content in Rosmarin. Analyst 2017; 142: 455-464
9 Wiedemair V, Huck CW. Evaluation of the performance of three hand-held near-infrared spectrometer through investigation of total antioxidant capacity in gluten- free grains. Talanta 2018; 189: 233-240
10 Schmutzler M, Huck CW. Simultaneous detection of total antioxidant capacity and total soluble solids content by Fourier transform near-infrared (FT-NIR) spectroscopy: a quick and sensitive method for on-site analyses of apples. Food Control 2016; 66: 27-37
11 Henn R, Kirchler CG, Grossgut ME, Huck CW. Comparison of sensitivity to artificial spectral errors and multivariate LOD in NIR spectroscopy – Determining the performance of miniaturizations on melamine in milk powder. Talanta 2017; 166: 109-118
12 Henn R, Kirchler CG, Huck CW. Miniaturized NIR spectroscopy for the determination of main carbohydrates in syrup. NIR news 2017; 28: 3-6
13 Koláčková P, Růžičková G, Gregor T, Šišperová E. Quick method (FT-NIR) for the determination of oil and major fatty acids content in whole achenes of milk thistle (Silybum marianum (L.) Gaertn.). J Sci Food Agric 2015; 95: 2264-2270
14 Pezzei CK, Schonbichler SA, Hussain S, Kirchler CG, Huck-Pezzei VA, Popp M, Krolitzek J, Bonn GK, Huck CW. Near-infrared and mid-infrared spectroscopic techniques for a fast and nondestructive quality control of Thymi herba. Planta Med 2018; 84: 420-427
15 Huck CW. Advances of infrared spectroscopy in natural product research. Phytochem Lett 2015; 11: 384-393
16 Pezzei CK, Schönbichler SA, Kirchler CG, Schmelzer J, Hussain S, Huck-Pezzei VA, Popp M, Krolitzek J, Bonn GK, Huck CW. Application of benchtop and portable near-infrared spectrometers for predicting the optimum harvest time of Verbena officinalis. Talanta 2017; 169: 70-76
17 Ibrahim AH, Smått JH, Govardhanam NP, Ibrahim HM, Ismael HR, Afouna MI, Samy AM, Rosenholm JM. Formulation and optimization of drug-loaded mesoporous silica nanoparticle-based tablets to improve the dissolution rate of the poorly water-soluble drug silymarin. Eur J Pharm Sci 2020; 142: 105103
18 Nazir S, Zaka M, Adil M, Abbasi BH, Hano C. Synthesis, characterisation and bactericidal effect of ZnO nanoparticles via chemical and bio-assisted (Silybum marianum in vitro plantlets and callus extract) methods: a comparative study. IET Nanobiotechnol 2018; 12: 604-608
19 Song JE, Jeon YS, Tian J, Kim WK, Choi MJ, Carlomagno C, Khang G. Evaluation of silymarin/duckʼs feet-derived collagen/hydroxyapatite sponges for bone tissue regeneration. Mater Sci Eng C 2019; 97: 347-355
20 Pantazi XE, Tamouridou AA, Alexandridis TK, Lagopodi AL, Kontouris G, Moshou D. Detection of Silybum marianum infection with Microbotryum silybum using VNIR field spectroscopy. Comput Electron Agric 2017; 137: 130-137
21 Tamouridou AA, Pantazi XE, Alexandridis T, Lagopodi A, Kontouris G, Moshou D. Spectral identification of disease in weeds using multilayer perceptron with automatic relevance determination. Sensors (Switzerland) 2018; 18: 2770
22 Zisi T, Alexandridis TK, Kaplanis S, Navrozidis I, Tamouridou AA, Lagopodi A, Moushou D, Polychronos V. Incorporating surface elevation information in UAV multispectral images for mapping weed patches. J Imaging 2018; 4: 132
23 Huck CW. Miniaturized MIR and NIR sensors for medicinal plant quality control. Spectrosc Online 2017; 32: 8-15
24 OʼBrien NA, Hulse CA, Friedrich DM, Van Milligen FJ, Von Gunten MK, Pfeifer F, Siesler HW. Miniature near-infrared (NIR) spectrometer engine for handheld applications. Proc SPIE 2012; 8374: 837404
25 Lutz OMD, Bonn GK, Rode BM, Huck CW. Reproducible quantification of ethanol in gasoline via a customized mobile near-infrared spectrometer. Anal Chim Acta 2014; 826: 61-68
26 Thermo Scientific. microPHAZIR User Manual. Accessed January 25, 2020 at: http://tools.thermofisher.com/content/sfs/manuals/microPHAZIR-User-Manual.pdf
27 Alcalà M, Blanco M, Moyano D, Broad NW, OʼBrien N, Friedirch D, Pfeifer F, Siesler HW. Qualitative and quantitative pharmaceutical analysis with a novel hand-held miniature near infrared spectrometer. J Near Infrared Spectrosc 2013; 21: 445-457
28 VIAVI Solution (Optical Security and Performance Products Group). MicroNIR Spectrometer 1700 vs. 2200 MicroNIR. 2012: 1-20 Accessed January 25, 2020 at: https://abcs.it/images/pdf/MicroNIR-1700-vs-2200-comparison-and-case-study.pdf
29 Antila J, Tuohiniemi M, Rissanen A, Kantojärvi U, Lahti M, Viherkanto K, Kaarre M, Malinen J. MEMS- and MOEMS-based near-Infrared Spectrometers. In: Meyers RA. ed. Encyclopedia of Analytical Chemistry. Chichester: Wiley; 2000: 1-36
30 Cheilari A, Sturm S, Intelmann D, Seger C, Stuppner H. Head-to-head comparison of ultra-high-performance liquid chromatography with diode array detection versus quantitative nuclear magnetic resonance for the quantitative analysis of the silymarin complex in Silybum marianum fruit extracts. J Agric Food Chem 2016; 64: 1618-1626
31 Clarke FC. Near-infrared Microscopy and Image Analysis for pharmaceutical Process Control [Thesis]. London: University of London; 2006
32 Mayr S, Schmelzer J, Kirchler CG, Pezzei CK, Beć KB, Grabska J, Huck CW. Theae nigrae folium: Comparing the analytical performance of benchtop and handheld near-infrared spectrometers. Talanta 2021; 221: 121165
33 Maxim Integrated Products, Inc.. Application Note 6433: Understanding Penetration Depth vs. Wavelength for Biosensor Applications. San Jose, CA, USA: Maxim Integrated Products, Inc.; 2018
34 Sagberg H. Micromechanical Optical Filters for Spectrometry [Thesis]. Oslo: University of Oslo; 2005
35 Beć KB, Huck CW. Breakthrough potential in near-infrared spectroscopy: Spectra simulation. A review of recent developments. Front Chem 2019; 7: 48
36 Beć KB, Grabska J, Huck CW, Czarnecki MA. Spectra-structure correlations in isotopomers of Ethanol (CX3CX2OX; X = H, D): Combined near-infrared and anharmonic computational study. Molecules 2019; 24: 2189
37 Workman JJ, Weyer L. Practical Guide and spectral Atlas for interpretive near-infrared Spectroscopy. 2nd ed.. ed. Boca Raton, Florida: CRC Press; 2012
38 Czarnecki MA, Morisawa Y, Futami Y, Ozaki Y. Advances in molecular structure and interaction studies using near-infrared spectroscopy. Chem Rev 2015; 115: 9707-9744
39 European Directorate for the Quality of Medicines & HealthCare. IINFORMATION LEAFLET Ph. Eur. Reference Standard; MILK THISTLE DRY EXTRACT HRS batch 2. Eur Pharmacopoeia (Ph Eur) 2016; 3
40 Fearn T. Chemometrics: an enabling tool for NIR. NIR News 2013; 16: 17-19
41 Fearn T. A look at some standard pre-treatments for spectra. NIR News 2013; 10: 10
42 Fearn T. Chemometric Space. Are two pretreatments better than one?. NIR News 2003; 14: 9-11
43 Kessler W. Multivariate Datenanalyse für die Pharma-, Bio- und Prozessanalytik. Weinheim: Wiley-VCH Verlag GmbH & Co.; 2007
44 Williams P, Dardenne P, Flinn P. Tutorial: Items to be included in a report on a near infrared spectroscopy project. J Near Infrared Spectrosc 2017; 25: 85-90
45 Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Petersson GA, Nakatsuji H, Li X, Caricato M, Marenich A, Bloino J, Janesko BG, Gomperts R, Mennucci B, Hratchian HP, Ortiz JV, Izmaylov AF, Sonnenberg JL, Williams-Young D, Ding F, Lipparini F, Egidi F, Goings J, Peng B, Petrone A, Henderson T, Ranasinghe D, Zakrzewski VG, Gao J, Rega N, Zheng G, Liang W, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Throssell K, Montgomery JA, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Keith T, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Millam JM, Klene M, Adamo C, Cammi R, Ochterski JW, Martin RL, Morokuma K, Farkas O, Foresman JB, Fox DJ. Gaussian 09, Revision E.01. Wallingford, CT: Gaussian, Inc.; 2009

Supplementary Material

Supporting Information