Journal of Applied Pharmaceutical Science Vol. 12(03), pp 191-201, March, 2022 Available online at http://www.japsonline.com DOI: 10.7324/JAPS.2022.120320 ISSN 2231-3354 INTRODUCTION Herbal medicine consumption was increasing due to its preventive and treatment functions. Claimed as safe, natural, and with minor adverse effects, herbal medicine has become a promising option to cure and maintain health conditions (de Carvalho Lopes and Neto, 2018; Ernst, 2002). However, there are some fndings of adulterated herbal medicine purposefully mixed by synthetic drugs in the market. The adulteration of herbal medicine phenomenon is an unacceptable action to accelerate the fast and effective effect (Popescu and Radu, 2015). Analgesic drugs such as metamizole, diclofenac sodium, and prednisone were commonly found in herbal medicine to reduce pain (Sanzini et al., 2011). The improper use of non-steroidal anti-infammation drugs and steroidal drugs could lead to undesirable adverse effects, in particular tachycardia, gastrointestinal disorder, hypertension, and hyperglycemia (Gan, 2010; Jin et al., 2018; Vijayalakshmi and Anbazhagan, 2011). Some countries from Asia, Europe, Africa, and America had a report about adulteration herbal medicine with a synthetic drug. Indonesia is one of the countries that have a high number of reports about this unethical incident. Some irresponsible manufactured herbal medicine products such as Jamu intentionally alloyed Jamu and synthetic drugs (Ariffn et al., 2021; Cebi et al., 2017; Ching et al., 2018; Snyman et al., 2005). The most used methods to detect synthetic drugs in herbal medicine are High performance liquid chromatography (HPLC), thin layer chromatography, LC-MS, and gas chromatography- mass spectrometer (Lee et al., 2017; Mustarichie et al., 2017; Popescu and Radu, 2015; Vijayalakshmi and Anbazhagan, 2011). A development method of FTIR spectroscopy coupled with chemometrics for detection of synthetic drug adulterants of herbal products in quaternary mixture Dharmastuti Cahya Fatmarahmi 1 , Ratna Asmah Susidarti 2 , Respati Tri Swasono 3 , Abdul Rohman 2,4 * 1 Doctoral Student in the Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia. 2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia. 3 Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Gadjah Mada, Yogyakarta, Indonesia. 4 Center of Excellence, Institute for Halal Industry and Systems (PUI-PT IHIS UGM), Universitas Gadjah Mada, Yogyakarta. ARTICLE INFO Received on: 25/08/2021 Accepted on: 11/11/2021 Available Online: 05/03/2022 Key words: Jamu, mid-infrared, multivariate analysis, counterfeit, analgesic drugs. ABSTRACT Fourier transform infrared-attenuated total refection (FTIR-ATR) spectroscopy, especially mid-infrared, has fulflled the need to counter the rising number of adulterated herbal products in society. The non-destructive, rapid, and inexpensive methods are criteria found in FTIR spectroscopy. This study aimed to develop a combination method between FTIR- ATR spectroscopy and chemometrics to analyze the quaternary model of adulterated herbal products claimed as analgesics. The samples consist of three types of analgesic herbal products (Jamu Pegal Linu, Jamu Encok, and Jamu Sakit Pinggang), prednisone, metamizole, diclofenac sodium, and quaternary mixtures were prepared and measured using FTIR spectrophotometer on absorbance mode at wavenumbers range 4,000–650 cm −1 . Principal Component Analysis (PCA), Partial Least Square Regression (PLSR), Principal Component Regression (PCR), and Discriminant Analysis were applied for analyzing spectra. The PCA result showed good differentiation between samples. The output of multivariate calibrations was excellent in line with statistical parameter value. The accuracy and precision from PLSR and PCR of quaternary mixtures were shown by a low value of root mean square error of prediction and root mean square error of calibration and R 2 > 0.99. Therefore, we suggested the combination method between FTIR-ATR and chemometrics as screening analytical technique to detect any adulterant drugs in herbal products. *Corresponding Author Abdul Rohman, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia. E-mail: abdul_kimfar @ ugm.ac.id © 2022 Dharmastuti Cahya Fatmarahmi et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).