Spectrophotometric methods for determination of naringin, amlodipine, and nifedipine using chemometric techniques

Authors

  • Vishala Rani Baraily Assam down town University, Panikhaiti, Guwahati, Assam, 781026, India
  • Jithendar Reddy Mandhadi Assam down town University, Panikhaiti, Guwahati, Assam, 781026, India
  • Bhupendra Shrestha Himalayan Pharmacy Institute, Majhitar, East Sikkim 737136, India

DOI:

https://doi.org/10.69857/joapr.v13i3.1107

Keywords:

Chemometrics, Naringin, Nifedipine, Amlodipine, UV-spectroscopy, Orthogonal partial least squares (OPLS)

Abstract

Background: Chemometrics articulates statistical and mathematical aspects to analyse the effectiveness of chemical data, playing a pivotal role in spectroscopy. Among all the chemometrics techniques, this study utilizes the Orthogonal partial least squares (OPLS) model for the simultaneous analysis of naringin, amlodipine, and nifedipine, a well-established calcium channel blocker. Naringin, a citrus flavonoid exhibiting notable pharmacological activities. Methodology: This research employs UV-visible spectrophotometry in conjunction with the OPLS method for both calibration and prediction sets in simultaneous studies of Amlodipine–Naringin and Nifedipine–Naringin, aiming to develop a precise model for measuring drug concentrations. A linear dynamic range of 5-20 µg/mL was achieved for standard solutions, while calibration sets were developed using factorial designs. Result and Discussion: The OPLS model had significant predictive performance with R2 values within the range of 0.9947-0.9976 for calibration and 0.9947-0.9985 for prediction, and low root mean square error of cross validation (RMSECV) values of 0.6191- 0.4353 for NIF-NAR, and 0.3978- 0.4418 for AML-NAR, indicating robust model performance. The model validation process, using Hotelling’s T2 test, DModx, established no significant outliers, and permutation analysis validated the model’s reliable fit. The recovery studies showed values close to 100%, thus verifying the effectiveness of the methodology. Conclusion: The research demonstrated OPLS (Orthogonal Partial Least Squares) as a powerful solution for resolving overlapping spectral data, providing high-precision drug analysis with minimal interference. The development of chemometrics methods demonstrated efficiency and precision in pharmaceutical analysis while also offering cost-effectiveness for quality control and formulation development.

Downloads

Download data is not yet available.

References

Héberger K. Chemoinformatics—multivariate mathematical–statistical methods for data evaluation. Medical Applications of Mass Spectrometry. Elsevier, pp. 141–69 (2008) https://doi.org/10.1016/B978-044451980-1.50009-4

Abraham EJ, Kellogg JJ. Chemometric-Guided Approaches for Profiling and Authenticating Botanical Materials. Front. Nutr., 8, 780228 (2021) https://doi.org/10.3389/fnut.2021.780228.

Popovic A, Morelato M, Roux C, Beavis A. Review of the most common chemometric techniques in illicit drug profiling. Forensic Science International, 302, 109911 (2019) https://doi.org/10.1016/j.forsciint.2019.109911

Brown SD, Blank TB, Sum ST, Weyer LG. Chemometrics. Anal. Chem., 66, 315–59 (1994) https://doi.org/10.1021/ac00084a014

Biancolillo A, Marini F. Chemometric Methods for Spectroscopy-Based Pharmaceutical Analysis. Front. Chem., 6, 576 (2018) https://doi.org/10.3389/fchem.2018.00576.

Abdelazim AH, Shahin M. Different chemometric assisted approaches for spectrophotometric quantitative analysis of lesinurad and allopurinol. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 251, 119421 (2021) https://doi.org/10.1016/j.saa.2020.119421.

Nurani LH, Edityaningrum CA, Irnawati I, Putri AR, Windarsih A, Guntarti A, Rohman A. Chemometrics-Assisted UV-Vis Spectrophotometry for Quality Control of Pharmaceuticals: A Review. Indonesian Journal of Chemistry, 23, 542–67 (2023) https://doi.org/10.22146/ijc.74329.

Coelho EM, Da Silva Haas IC, De Azevedo LC, Bastos DC, Fedrigo IMT, Dos Santos Lima M, De Mello Castanho Amboni RD. Multivariate chemometric analysis for the evaluation of 22 Citrus fruits growing in Brazil’s semi-arid region. Journal of Food Composition and Analysis, 101, 103964 (2021) https://doi.org/10.1016/j.jfca.2021.103964.

Zulkifli B, Fakri F, Odigie J, Nnabuife L, Isitua CC, Chiari W. Chemometric-empowered spectroscopic techniques in pharmaceutical fields: A bibliometric analysis and updated review. Narra X, 1, (2023) https://doi.org/10.52225/narrax.v1i1.80.

Mostafa A, Shaaban H. Chemometric Assisted UV-Spectrophotometric Methods Using Multivariate Curve Resolution Alternating Least Squares and Partial Least Squares Regression for Determination of Beta-Antagonists in Formulated Products: Evaluation of the Ecological Impact. Molecules, 28, 328 (2023) https://doi.org/10.3390/molecules28010328.

Zeid AM, Abdelazim AH, Shahin M. Simultaneous spectrophotometric quantitative analysis of elbasvir and grazoprevir using assisted chemometric models. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 252, 119505 (2021) https://doi.org/10.1016/j.saa.2021.119505.

Boccard J, Rutledge DN. A consensus orthogonal partial least squares discriminant analysis (OPLS-DA) strategy for multiblock Omics data fusion. Analytica Chimica Acta, 769, 30–9 (2013) https://doi.org/10.1016/j.aca.2013.01.022.

Abdelazim AH, Shahin M, Abu-khadra AS. Application of different chemometric assisted models for spectrophotometric quantitative analysis of velpatasvir and sofosbuvir. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 252, 119540 (2021) https://doi.org/10.1016/j.saa.2021.119540.

Bylesjö M, Eriksson D, Sjödin A, Jansson S, Moritz T, Trygg J. Orthogonal projections to latent structures as a strategy for microarray data normalization. BMC Bioinformatics, 8, 207 (2007) https://doi.org/10.1186/1471-2105-8-207.

Gabrielsson J, Jonsson H, Airiau C, Schmidt B, Escott R, Trygg J. OPLS methodology for analysis of pre-processing effects on spectroscopic data. Chemometrics and Intelligent Laboratory Systems, 84, 153–8 (2006) https://doi.org/10.1016/j.chemolab.2006.03.013.

Forsgren E, Björkblom B, Trygg J, Jonsson P. OPLS-Based Multiclass Classification and Data-Driven Interclass Relationship Discovery. J. Chem. Inf. Model., 65, 1762–70 (2025) https://doi.org/10.1021/acs.jcim.4c01799.

Bylesjö M, Rantalainen M, Cloarec O, Nicholson JK, Holmes E, Trygg J. OPLS discriminant analysis: combining the strengths of PLS‐DA and SIMCA classification. Journal of Chemometrics, 20, 341–51 (2006) https://doi.org/10.1002/cem.1006.

Trygg J, Wold S. Orthogonal projections to latent structures (O‐PLS). Journal of Chemometrics, 16, 119–28 (2002) https://doi.org/10.1002/cem.695.

Silva LCRC e, David JM, Borges R dos SQ, Ferreira SLC, David JP, Reis PS dos, Bruns RE. Determination of Flavanones in Orange Juices Obtained from Different Sources by HPLC/DAD. Journal of Analytical Methods in Chemistry, 2014, 296838 (2014) https://doi.org/10.1155/2014/296838.

Ribeiro IA, Ribeiro MHL. Naringin and naringenin determination and control in grapefruit juice by a validated HPLC method. Food Control, 19, 432–8 (2008) https://doi.org/10.1016/j.foodcont.2007.05.007.

Jung UJ, Kim SR. Effects of naringin, a flavanone glycoside in grapefruits and citrus fruits, on the nigrostriatal dopaminergic projection in the adult brain. Neural Regeneration Research, 9, 1514 (2014) https://doi.org/10.4103/1673-5374.139476.

EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP). Scientific Opinion on the safety and efficacy of naringin when used as a sensory additive for all animal species. EFSA Journal, 9, 2416 (2011) https://doi.org/10.2903/j.efsa.2011.2416.

Gunes A, and Dahl M-L. Variation in CYP1A2 Activity and its Clinical Implications: Influence of Environmental Factors and Genetic Polymorphisms. Pharmacogenomics, 9, 625–37 (2008) https://doi.org/10.2217/14622416.9.5.625.

Van Geijn HP, Lenglet JE, Bolte AC. Nifedipine trials: effectiveness and safety aspects. BJOG, 112, 79–83 (2005) https://doi.org/10.1111/j.1471-0528.2005.00591.x.

Freedman DD, Waters DD. ‘Second Generation’ Dihydropyridine Calcium Antagonists. Drugs, 34, 578–98 (1987) https://doi.org/10.2165/00003495-198734050-00005.

Curtis TM, Scholfield CN. Nifedipine blocks Ca2+ store refilling through a pathway not involving L-type Ca2+ channels in rabbit arteriolar smooth muscle. J Physiol, 532, 609–23 (2001) https://doi.org/10.1111/j.1469-7793.2001.0609e.x.

Kaya H, Polat B, Albayrak A, Mercantepe T, Buyuk B. Protective effect of an L-type calcium channel blocker, amlodipine, on paracetamol-induced hepatotoxicity in rats. Hum Exp Toxicol, 37, 1169–79 (2018) https://doi.org/10.1177/0960327118758382.

Höcht C, Bertera ,Facundo M., Santander Plantamura ,Yanina, Parola ,Luciano, Del Mauro ,Julieta S., and Polizio AH. Factors influencing hepatic metabolism of antihypertensive drugs: impact on clinical response. Expert Opinion on Drug Metabolism & Toxicology, 15, 1–13 (2019) https://doi.org/10.1080/17425255.2019.1558204.

Zhang Y-P, Zuo X-C, Huang Z-J, Cai J-J, Wen J, Duan DD, Yuan H. CYP3A5 polymorphism, amlodipine and hypertension. J Hum Hypertens, 28, 145–9 (2014) https://doi.org/10.1038/jhh.2013.67.

Guo Y, Lucksiri A, Dickinson GL, Vuppalanchi RK, Hilligoss JK, Hall SD. Quantitative Prediction of CYP3A4‐ and CYP3A5‐Mediated Drug Interactions. Clin Pharma and Therapeutics, 107, 246–56 (2020) https://doi.org/10.1002/cpt.1596.

Zhu Y, Wang F, Li Q, Zhu M, Du A, Tang W, Chen W. Amlodipine Metabolism in Human Liver Microsomes and Roles of CYP3A4/5 in the Dihydropyridine Dehydrogenation. Drug Metab Dispos, 42, 245–9 (2014) https://doi.org/10.1124/dmd.113.055400.

Yeum C-H, Choi J-S. Effect of naringin pretreatment on bioavailability of verapamil in rabbits. Arch Pharm Res, 29, 102–7 (2006) https://doi.org/10.1007/BF02977476.

Choi J-S, Li X. Enhanced diltiazem bioavailability after oral administration of diltiazem with quercetin to rabbits. International Journal of Pharmaceutics, 297, 1–8 (2005) https://doi.org/10.1016/j.ijpharm.2004.12.004.

Branch SK. Guidelines from the International Conference on Harmonisation (ICH). Journal of Pharmaceutical and Biomedical Analysis, 38, 798–805 (2005) https://doi.org/10.1016/j.jpba.2005.02.037.

Sonawane SS, Chhajed SS, Attar SS, Kshirsagar SJ. An approach to select linear regression model in bioanalytical method validation. J Anal Sci Technol, 10, 1 (2019) https://doi.org/10.1186/s40543-018-0160-2.

Abdallah FF, Darwish HW, Darwish IA, Naguib IA. Orthogonal projection to latent structures and first derivative for manipulation of PLSR and SVR chemometric models’ prediction: A case study. PLoS ONE, 14, e0222197 (2019) https://doi.org/10.1371/journal.pone.0222197.

Ríos-Reina R, Azcarate SM. How Chemometrics Revives the UV-Vis Spectroscopy Applications as an Analytical Sensor for Spectralprint (Nontargeted) Analysis. Chemosensors, 11, 8 (2023) https://doi.org/10.3390/chemosensors11010008.

Sharma S, Shrestha B, Bhuyan NR, Majumdar S, Chowdhury S, Mazumder R. Chemometric method development for the determination of naringin and verapamil. Bull Natl Res Cent, 48, 13 (2024) https://doi.org/10.1186/s42269-024-01169-3.

Khatib S, Daoutidis P. Multiple Hotelling’s T2 tests for distributed fault detection of large-scale systems. Computers & Chemical Engineering, 136, 106807 (2020) https://doi.org/10.1016/j.compchemeng.2020.106807.

Li Z, Yu Y, Pan X, Karim MN. Effect of dataset size on modeling and monitoring of chemical processes. Chemical Engineering Science, 227, 115928 (2020) https://doi.org/10.1016/j.ces.2020.115928.

Eriksson L, Trygg J, Wold S. CV-ANOVA for significance testing of PLS and OPLS® models. Journal of Chemometrics, 22, 594–600 (2008) https://doi.org/10.1002/cem.1187.

Bagherian G, Salehi Mobarake F, Arab Chamjangali M, Ashrafi M, Borzooei H. Comparison between univariate and multivariate calibration methods for simultaneous spectrophotometric determination of catechol and hydroquinone in their binary mixture. Frontiers in Chemical Research, 2, 1–9 (2020) https://doi.org/10.22034/fcr.2020.116897.1011.

Lotfy HM, Saleh SS, Hassan NY, Elgizawy SM. A Comparative Study of the Novel Ratio Difference Method versus Conventional Spectrophotometric Techniques for the Analysis of Binary Mixture with Overlapped Spectra. American Journal of Analytical Chemistry, 3, 761–9 (2012) https://doi.org/10.4236/ajac.2012.311101.

Lotfy HM, Hegazy MA, Rezk MR, Omran YR. Comparative study of novel versus conventional two-wavelength spectrophotometric methods for analysis of spectrally overlapping binary mixture. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 148, 328–37 (2015) https://doi.org/10.1016/j.saa.2015.04.004.

Pierce KM, Kehimkar B, Marney LC, Hoggard JC, Synovec RE. Review of chemometric analysis techniques for comprehensive two dimensional separations data. Journal of Chromatography A, 1255, 3–11 (2012) https://doi.org/10.1016/j.chroma.2012.05.050.

Darwish HW, Backeit AH. Multivariate Versus Classical Univariate Calibration Methods for Spectrofluorimetric Data: Application to Simultaneous Determination of Olmesartan Medoxamil and Amlodipine Besylate in their Combined Dosage Form. J Fluoresc, 23, 79–91 (2013) https://doi.org/10.1007/s10895-012-1119-0.

Faber N (Klaas) M. Estimating the uncertainty in estimates of root mean square error of prediction: application to determining the size of an adequate test set in multivariate calibration. Chemometrics and Intelligent Laboratory Systems, 49, 79–89 (1999) https://doi.org/10.1016/S0169-7439(99)00027-1.

Kościelniak P, Wieczorek M. Univariate analytical calibration methods and procedures. A review. Analytica Chimica Acta, 944, 14–28 (2016) https://doi.org/10.1016/j.aca.2016.09.024.

Roy PP, Roy K. On Some Aspects of Variable Selection for Partial Least Squares Regression Models. QSAR Comb. Sci., 27, 302–13 (2008) https://doi.org/10.1002/qsar.200710043.

Published

2025-06-30

How to Cite

Baraily, V. R., Mandhadi, J. R. ., & Shrestha, B. . (2025). Spectrophotometric methods for determination of naringin, amlodipine, and nifedipine using chemometric techniques. Journal of Applied Pharmaceutical Research, 13(3), 154-163. https://doi.org/10.69857/joapr.v13i3.1107

Issue

Section

Articles