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Current Pharmaceutical Analysis

Author(s): Mario Theodore and Vorasit Vongsutilers*

DOI: 10.2174/0115734129295505240430092112

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Development of Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy Coupled with Multivariate Classification Chemometric Model for Routine Screening of Paracetamol, Ibuprofen, and Aspirin Adulteration in Herbal Products

Page: [283 - 297] Pages: 15

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Abstract

Objective: The objective of this study is to develop and validate a routine screening test for the determination of three common antipyretic-analgesic synthetic drugs (paracetamol, ibuprofen, and aspirin) adulteration in herbal products using Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) coupled with chemometric method.

Methods: ATR-FTIR spectra of sixteen testing sets of herbal product samples for pain and fever indications were used for multivariate chemometrics model construction. Linear Discriminant Analysis (LDA) was selected as a method for model construction with IBM SPSS for statistical analysis. Model development employed feature selection, such as the stepwise method for variable selection. The model with a high %correct classification and cross-validation was selected and was then validated with an independent testing data set with an auto-prediction test, confusion matrix, and Receiver Operating Characteristic (ROC) curve. To validate the developed test for routine use, the result from ATR-FTIR method was compared with the standard HPLC and TLC analyses used for adulteration screening.

Results: The selected model's overall %correct classification result was 97.7%, with a cross-validation of 93.8% rate in training set samples. External validation with an independent testing dataset gave an overall correct classification of 93.8%, with an area under the curve of ROC at 0.979. Comparative testing revealed that model performance was comparable with the HPLC and TLC methods, which routinely detect the presence of paracetamol, aspirin, and ibuprofen. The results of testing set samples classification were consistent with training set samples.

Conclusion: Against the standard chromatographic methods, the multivariate chemometric model based on ATR-FTIR demonstrates comparable detection capability to determine adulteration of paracetamol, ibuprofen, and aspirin in herbal products.

Graphical Abstract

[1]
WHO. Regulatory Status Of Herbal Medicines.In: Who, Editor. Who Global Report On Traditional And Complementary Medicine 2019; Luxembourg: WHO, 2019, pp. 1-29.
[2]
WHO. WHO monographs on selected medicinal plants; Spain, 2006, 3, pp. 416-422.
[3]
Liu, C. Overview on development of ASEAN traditional and herbal medicines. Chin. Herb. Med., 2021, 13(4), 441-450.
[http://dx.doi.org/10.1016/j.chmed.2021.09.002] [PMID: 36119367]
[4]
BPOM. Bab 1 Ketentuan Umum. Peraturan Kepala Badan Pengawas Obat Dan Makanan Republik Indonesia Nomor: Hk.00.05.41.1384 Tentang Kriteria Dan Tata Laksana Pendaftaran Obat Tradisional, Obat Herbal Terstandar Dan Fitofarmaka, HK.00.05.41.1384; BPOM: Jakarta, Indonesia, 2005.
[5]
Ur Rehman, M.; Akram, M.; Naveed, A. Zingiber officinale Roscoe (pharmacological activity). J. Med. Plants Res., 2010, 11/30, 5.
[6]
Mashhadi, N.S.; Ghiasvand, R.; Askari, G.; Hariri, M.; Darvishi, L.; Mofid, M.R. Anti-oxidative and anti-inflammatory effects of ginger in health and physical activity: review of current evidence. Int. J. Prev. Med., 2013, 4(Suppl. 1), S36-S42.
[PMID: 23717767]
[7]
Karunakaran, R.; Sadanandan, S.P. Zingiber officinale: Antiinflammatory actions and potential usage for arthritic conditions. In: Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases (Second Edition); Watson, RR; Preedy, VR., Eds.; Academic Press, 2019; pp. 233-244.
[8]
Terry, R.; Posadzki, P.; Watson, L.K.; Ernst, E. The use of ginger (Zingiber officinale) for the treatment of pain: a systematic review of clinical trials. Pain Med., 2011, 12(12), 1808-1818.
[http://dx.doi.org/10.1111/j.1526-4637.2011.01261.x] [PMID: 22054010]
[9]
Diastuti, H.; Syah, Y.; Juliawaty, L. Antibacterial activity of germacrone sesquiterpene from curcuma xanthorrhiza rhizomes. ALCHEMY J. Penelitian Kimia, 2016, 12-18.
[10]
Tan, T.; Huang, Q.; Chu, W.; Li, B.; Wu, J.; Xia, Q.; Cao, X. Delivery of germacrone (GER) using macrophages-targeted polymeric nanoparticles and its application in rheumatoid arthritis. Drug Deliv., 2022, 29(1), 692-701.
[http://dx.doi.org/10.1080/10717544.2022.2044936] [PMID: 35225122]
[11]
Chan, C.K.; Tan, L.T.H.; Andy, S.N.; Kamarudin, M.N.A.; Goh, B.H.; Kadir, H.A. Anti-neuroinflammatory Activity of Elephantopus scaber L. via Activation of Nrf2/HO-1 Signaling and Inhibition of p38 MAPK Pathway in LPS-Induced Microglia BV-2 Cells. Front. Pharmacol., 2017, 8, 397.
[http://dx.doi.org/10.3389/fphar.2017.00397] [PMID: 28680404]
[12]
Nurtamin, T.; Sudayasa, I. In Vitro anti-inflammatory activities of ethanolic extract elephantopus scaber leaves. J. Kedokteran dan Kesehatan Indonesia., 2018, 04/30(9), 46-52.
[13]
Qi, R.; Li, X.; Zhang, X.; Huang, Y.; Fei, Q.; Han, Y.; Cai, R.; Gao, Y.; Qi, Y. Ethanol extract of Elephantopus scaber Linn. Attenuates inflammatory response via the inhibition of NF-κB signaling by dampening p65-DNA binding activity in lipopolysaccharide-activated macrophages. J. Ethnopharmacol., 2020, 250, 112499.
[http://dx.doi.org/10.1016/j.jep.2019.112499] [PMID: 31877363]
[14]
Shaari, A. Overview of Medicinal Plants spread and their uses in Asia; University Perlis Malaysia, 2020, pp. 1-8.
[15]
Ernst, E. Adulteration of Chinese herbal medicines with synthetic drugs: A systematic review. J. Intern. Med., 2002, 252(2), 107-113.
[http://dx.doi.org/10.1046/j.1365-2796.2002.00999.x] [PMID: 12190885]
[16]
Ekar, T.; Kreft, S. Common risks of adulterated and mislabeled herbal preparations. Food Chem. Toxicol., 2019, 123, 288-297.
[http://dx.doi.org/10.1016/j.fct.2018.10.043] [PMID: 30339960]
[17]
Ernst, E. Pharmacokinetic interactions between herbal medicines and drugs: Their mechanisms and clinical relevance. 2000.
[18]
Posadzki, P.; Watson, L.; Ernst, E. Contamination and adulteration of herbal medicinal products (HMPs): An overview of systematic reviews. Eur. J. Clin. Pharmacol., 2013, 69(3), 295-307.
[http://dx.doi.org/10.1007/s00228-012-1353-z] [PMID: 22843016]
[19]
Ariffin, S.H.; A Wahab, I.; Hassan, Y.; Abd Wahab, M.S. Adulterated traditional-herbal medicinal products and its safety signals in malaysia. Drug Healthc. Patient Saf., 2021, 13, 133-140.
[http://dx.doi.org/10.2147/DHPS.S305953] [PMID: 34135639]
[20]
Pharmacokinetic Interactions between Herbal Medicines and Drugs: Their Mechanisms and Clinical Relevance. Available from: https://e-publicwarningotsk.pom.go.id/pw2022/#statbx
[21]
Acetaminophen 2022. Available from: https://www.drugs.com/acetaminophen.html
[22]
Yoon, E.; Babar, A.; Choudhary, M.; Kutner, M.; Pyrsopoulos, N. Acetaminophen-induced hepatotoxicity: a Comprehensive Update. J. Clin. Transl. Hepatol., 2016, 4(2), 131-142.
[PMID: 27350943]
[23]
Ibuprofen 2022. Available from: https://www.drugs.com/ibuprofen.html
[24]
Mărginean, M.O.; Meliț, L.E.; Mocanu, S.; Săsăran, V. Ibuprofen, a potential cause of acute hemorrhagic gastritis in children : A case report. J. Crit. Care Med., 2018, 4(4), 143-146.
[http://dx.doi.org/10.2478/jccm-2018-0022] [PMID: 30574567]
[25]
Calahan, J.; Howard, D.; Almalki, A.; Gupta, M.; Calderón, A. Chemical adulterants in herbal medicinal products: A review. Planta Med., 2016, 82(6), 505-515.
[http://dx.doi.org/10.1055/s-0042-103495] [PMID: 27054916]
[26]
Li, Z.; Wang, Z.; Shen, B.; Chen, C.; Ding, X.; Song, H. Effects of aspirin on the gastrointestinal tract: Pros vs. cons (Review). Oncol. Lett., 2020, 20(3), 2567-2578.
[http://dx.doi.org/10.3892/ol.2020.11817] [PMID: 32782574]
[27]
Philp, M.; Fu, S. A review of chemical ‘spot’ tests: A presumptive illicit drug identification technique. Drug Test. Anal., 2018, 10(1), 95-108.
[http://dx.doi.org/10.1002/dta.2300] [PMID: 28915346]
[28]
Robi’atul Andawiyah; Satriawan, N.E.; Jumaati Fabrication of test strip for sibutramine hcl detection in slimming traditional herbal medicine. J. Kimia Riset, 2023, 8(1), 27-36.
[http://dx.doi.org/10.20473/jkr.v8i1.41110]
[29]
Noviana, E.; Carrão, D.B.; Pratiwi, R.; Henry, C.S. Emerging applications of paper-based analytical devices for drug analysis: A review. Anal. Chim. Acta, 2020, 1116, 70-90.
[http://dx.doi.org/10.1016/j.aca.2020.03.013] [PMID: 32389191]
[30]
Pratiwi, R.; Dipadharma, R.H.F.; Prayugo, I.J.; Layandro, O.A. Recent analytical method for detection of chemical adulterants in herbal medicine. Molecules, 2021, 26(21), 6606.
[http://dx.doi.org/10.3390/molecules26216606] [PMID: 34771013]
[31]
Hemdan, A.; Tawakol, S.M. HPLC–UV chromatographic methods for detection and quantification of undeclared withdrawn synthetic medications in counterfeit herbal medicines with confirmation by HPLC–PDA and mass spectrometry. Chromatographia, 2018, 81(5), 777-783.
[http://dx.doi.org/10.1007/s10337-018-3502-8]
[32]
Ko, K.Y.; Choi, E.Y.; Jeong, S.H.; Kim, S.; Lee, C-K.; Lee, C.; Cho, S. Simple HPLC-PDA analysis to determine illegal synthetic dyes in herbal medicines. Appl. Sci., 2021, 11(14), 6641.
[http://dx.doi.org/10.3390/app11146641]
[33]
Govindarajan, R.; Tejas, V.; Pushpangadan, P. High-performance liquid chromatography (HPLC) as a tool for standardization of complex herbal drugs. J. AOAC Int., 2019, 102(4), 986-992.
[http://dx.doi.org/10.5740/jaoacint.18-0378] [PMID: 30558698]
[34]
Mwankuna, C; Mabiki, F; Mariki, E Thin layer chromatographic method for detection of conventional drug adulterants in herbal products. separations., 2022, 12/31, 10.
[35]
Minh, D.T.C.; Thi, L.A.; Huyen, N.T.T.; Van Vu, L.; Anh, N.T.K.; Ha, P.T.T. Detection of sildenafil adulterated in herbal products using thin layer chromatography combined with surface enhanced Raman spectroscopy: “Double coffee-ring effect” based enhancement. J. Pharm. Biomed. Anal., 2019, 174, 340-347.
[http://dx.doi.org/10.1016/j.jpba.2019.05.043] [PMID: 31202876]
[36]
Limmatvapirat, C.; Burana-osot, J.; Laopoonpat, P. Determination of dexamethasone and prednisolone adulterated in herbal medicines using thin-layer chromatography. Res. J. Pharm. Biol. Chem. Sci., 2012, 3, 1353-1358.
[37]
Bunaciu, A.A.; Aboul-Enein, H.Y.; Fleschin, S. Application of Fourier Transform Infrared Spectrophotometry in Pharmaceutical Drugs Analysis. Appl. Spectrosc. Rev., 2010, 45(3), 206-219.
[http://dx.doi.org/10.1080/00387011003601044]
[38]
Rohman, A. Application of fourier transform infrared spectroscopy for quality control of pharmaceutical products: A review. Indones. J. Pharm., 2012, 23(01), 1.
[39]
Brereton, R.G. Multiclass Classifiers. In: Chemometric of Pattern Recognition; John Wiley and Sons, Ltd, 2009; pp. 289-304.
[40]
Biancolillo, A.; Marini, F.; Ruckebusch, C.; Vitale, R. Chemometric strategies for spectroscopy-based food authentication. Appl. Sci., 2020, 10(18), 6544.
[http://dx.doi.org/10.3390/app10186544]
[41]
Noviana, E.; Indrayanto, G.; Rohman, A. Advances in fingerprint analysis for standardization and quality control of herbal medicines. Front. Pharmacol., 2022, 13, 853023.
[http://dx.doi.org/10.3389/fphar.2022.853023] [PMID: 35721184]
[42]
Foschi, M.; Tozzi, L.; Di Donato, F.; Biancolillo, A.; D’Archivio, A.A. A novel FTIR-based chemometric solution for the assessment of saffron adulteration with non-fresh stigmas. Molecules, 2022, 28(1), 33.
[http://dx.doi.org/10.3390/molecules28010033] [PMID: 36615229]
[43]
Dharmastuti Cahya, F.; Ratna Asmah, S.; Respati Tri, S. Application of ftir-atr spectroscopy in combination with multivariate analysis to analyse synthetic drugs adulterant in ternary mixtures of herbal medicine products. Indones. J. Pharm., 2022, 33(1), 2-8.
[44]
Chen, Y.; Zou, C.; Mastalerz, M.; Hu, S.; Gasaway, C.; Tao, X. Applications of micro-fourier transform infrared spectroscopy (FTIR) in the geological sciences : A review. Int. J. Mol. Sci., 2015, 16(12), 30223-30250.
[http://dx.doi.org/10.3390/ijms161226227] [PMID: 26694380]
[45]
Aspirin dosage 2021.Available from: https://www.drugs.com/dosage/aspirin.html
[46]
Corp, T.E. OMNIC Users Guide Version 7.3; Thermo Electron Corporation, 2006, pp. 1-8.
[47]
Chatfield, C.; Collins, A. Chapter Three Preliminary Data Analysis; Introduction to Multivariate Analysis, 2018, pp. 34-36.
[48]
Owen, A.J. Uses of Derivative Spectroscopy; Agilent Technology Inc., 1995, pp. 22-36.
[49]
PPPOMN. BPOM. MA 24/OT/11; BPOM: Jakarta, 2011.
[50]
PPOMN. BPOM. MA 01/OT/12; BPOM: Jakarta, 2012.
[51]
Grdadolnik, J. ATR-FTIR spectroscopy: Its advantages and limitations. Acta Chimica Slovenica., 2002, 49, 631-642.
[52]
Pavia, D.L. Infrared spectroscopy. In: Introduction to spectroscopy; Western Washington University: Bellingham, Washington, 2015.
[53]
Habiba, U.; Alam, A.; Rahman, S.; Shamim, S.U.D.; Piya, A.A. IR spectra of paracetamol. Bangladesh J. Sci. Ind. Res., 2021, 56(4), 255-262.
[http://dx.doi.org/10.3329/bjsir.v56i4.57197]
[54]
Pharmacopoeia, U.S. 1225<Validation of Compendial Procedures> USP-NF; United States Pharmacopoeia: United States, 2022.
[55]
Griffiths, P.; Haseth, J. Signal-to-noise ratio. In: Fourier Transform Infrared Spectrometry, 2nd; Wiley, 2006; pp. 06-08.
[56]
Oliveri, P.; Forina, M. Data Analysis and Chemometrics. Chemical Analysis of Food: Techniques and Applications., 2012, 31, 25.
[http://dx.doi.org/10.1016/B978-0-12-384862-8.00002-9]
[57]
Jamwal, R.; Amit; Kumari, S.; Sharma, S.; Kelly, S.; Cannavan, A.; Singh, D.K. Recent trends in the use of FTIR spectroscopy integrated with chemometrics for the detection of edible oil adulteration. Vib. Spectrosc., 2021, 113, 103222.
[58]
Corp. I.. Chapter 1 Core Features. In: IBM, editor. IBM SPSS Statistics Base 28;
[59]
Zhao, H.; Lai, Z.; Leung, H. Linear Discriminant Analysis. Feature Learning and Understanding, Algorithms and Applications; Shenzhen University: Shenzhen, China, 2020, pp. 71-85.
[60]
Mark, H.; Workman, J. The Statistics of Spectral Searches.Chemometrics in Spectroscopy, 2nd ed; Mark, H.; Workman, J., Eds.; Academic Press, 2018, pp. 507-511.

[61]
Pharmacopoeia, U.S. 1039 <Chemometrics>. USP-NF; United States Pharmacopeia: United States, 2022.
[62]
Florkowski, C.M. Sensitivity, specificity, receiver-operating characteristic (ROC) curves and likelihood ratios: communicating the performance of diagnostic tests. Clin. Biochem. Rev., 2008, 29(Suppl 1)(Suppl. 1), S83-S87.
[PMID: 18852864]
[63]
Fawcett, T. An introduction to ROC analysis. Pattern Recognit. Lett., 2006, 27(8), 861-874.
[http://dx.doi.org/10.1016/j.patrec.2005.10.010]
[64]
Pharmacopoeia, U.S. 621 <Chromatography>. USP-NF; United States Pharmacopoeia: United States, 2022.
[65]
Miao, L.; Liu, Y.; Li, H. Two-dimensional correlation infrared spectroscopy applied to the identification of ephedrine and pseudoephedrine in illegally adulterated slimming herbal products. Drug Test. Anal., 2016, 02/18, 9.
[PMID: 26888635]
[66]
Cebi, N.; Yilmaz, M.T.; Sagdic, O. A rapid ATR-FTIR spectroscopic method for detection of sibutramine adulteration in tea and coffee based on hierarchical cluster and principal component analyses. Food Chem., 2017, 229, 517-526.
[http://dx.doi.org/10.1016/j.foodchem.2017.02.072] [PMID: 28372210]
[67]
Azminah, A.; Ahmad, I.; Azmi, J. Rapid Detection of Synthetic Adulterants in Indonesian Herbal Medicines using ATR-FTIR Spectroscopy Combined with Chemometrics. Journal of Research in Pharmacy., 2023, 01(01), 184-195.
[68]
KEMENKUMHAM. Bagian Kelima Belas Pengamanan dan Penggunaan Sediaan Farmasi dan Alat Kesehatan. UNDANG-UNDANG REPUBLIK INDONESIA NOMOR 36 TAHUN 2009 TENTANG KESEHATAN; KEMENKUMHAM: Jakarta, Indonesia, 2009.
[69]
BPOM. Bab II Kategori Temuan. Peraturan Badan Pengawas Obat Dan Makanan Nomor 19 Tahun 2021 Tentang Pedoman Tindak Lanjut Hasil Pengawasan Obat Tradisional, Obat Kuasi, Suplemen Kesehatan, Dan Kosmetika; BPOM: Jakarta, Indonesia, 2019.
[70]
Berrar, D. Cross-Validation.Encyclopedia of Bioinformatics and Computational Biology; Ranganathan, S.; Gribskov, M.; Nakai, K., Eds.; Academic Press: Oxford, 2019, pp. 542-545.
[http://dx.doi.org/10.1016/B978-0-12-809633-8.20349-X]
[71]
Lavine, B.K. 3.20 - Feature Selection: Introduction.Comprehensive Chemometrics; Brown, S.D.; Tauler, R.; Walczak, B., Eds.; Elsevier: Oxford, 2009, pp. 601-607.
[http://dx.doi.org/10.1016/B978-044452701-1.00028-4]
[72]
Tharwat, A.; Gaber, T.; Ibrahim, A.; Hassanien, A.E. Linear discriminant analysis: A detailed tutorial. AI Commun., 2017, 30(2), 169-190.
[http://dx.doi.org/10.3233/AIC-170729]
[73]
Arif Nur, I.; Fella, S.; Mabrurotul, M.; Abdul, R. Implementation of chemometrics as a Solution to detecting and preventing falsification of herbal medicines in Southeast Asia: A review. J. Appl. Pharm. Sci., 2021.
[http://dx.doi.org/10.7324/JAPS.2021.110917]
[74]
Fan, J.; Upadhye, S.; Worster, A. Understanding receiver operating characteristic (ROC) curves. CJEM, 2006, 8(1), 19-20.
[http://dx.doi.org/10.1017/S1481803500013336] [PMID: 17175625]
[75]
Grandini, M; Bagli, E; Visani, G. Metrics for multi-class classification: An overview. arXiv:2008.05756, 2020.