SPECTROPHOTOMETRIC CO-ESTIMATION OF ATORVASTATIN AND EZETIMIBE IN A BINARY MIXTURE USING PRINCIPLE COMPONENT REGRESSION AND PARTIAL LEAST SQUARES REGRESSION MODELS

Zehra Ceren Ertekin; Erdal Dinç

doi:10.33483/jfpau.1666211

Research Article

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TEMEL BİLEŞEN REGRESYONU VE KISMİ EN KÜÇÜK KARELER REGRESYONU MODELLERİ KULLANILARAK ATORVASTATİN VE EZETİMİBİN İKİLİ KARIŞIMLARDA EŞZAMANLI TAYİNİ

Year 2025, Volume: 49 Issue: 3, 827 - 837, 19.09.2025

Zehra Ceren Ertekin , Erdal Dinç

https://doi.org/10.33483/jfpau.1666211

Abstract

Amaç: Atorvastatin (AT) ve ezetimibin (EZ) kombinasyonu gibi sabit dozlu formülasyonlardaki etken maddelerin spektral örtüşmeleri, UV-GB spektroskopi temelli analiz yöntemlerinin geliştirilmesini zorlaştırır. Geleneksel kromatografik yöntemler bu tür durumlarda etkili olsa da, maliyet açısından verimli değildir ve gerekli cihazlara erişim kolay olmayabilir. Bu çalışma, sabit dozlu formülasyonlarda AT ve EZ'in eş zamanlı miktar tayini için daha basit ve ekonomik bir spektrofotometri temelli yaklaşım geliştirmeyi amaçlamaktadır.
Gereç ve Yöntem: Bu çalışmada, temel bileşen regresyonu (PCR) ve kısmi en küçük kareler regresyonu (PLS) modelleri, UV-GB spektroskopisi ile birlikte kullanılmıştır. Her iki ilaç için de 4–36 µg/ml çalışma aralığında ikili karışımlardan oluşan bir kalibrasyon seti hazırlanmıştır. PCR ve PLS modelleri üç gizli değişken kullanılarak oluşturulmuştur. Geliştirilen yöntemler, laboratuvarda hazırlanan örnekler kullanılarak doğruluk, kesinlik ve seçicilik açısından değerlendirilmiştir. Yöntemlerin uygulanabilirliği, ticari tablet örnekleri analiz edilerek gösterilmiştir.
Sonuç ve Tartışma: Her iki modelle yüksek geri kazanım oranları (%98–102.3) ve düşük bağıl standart sapma değerleri (<%2.0) elde edilmiş, yöntemlerin doğruluk ve kesinliklerini doğrulamıştır. Yöntemlerin seçiciliği, standart ekleme çalışmaları ile teyit etmiştir. Kapsamlı numune hazırlama gerektirmeden, PCR ve PLS yöntemleri kullanılarak film kaplı tabletlerdeki AT ve EZ'in eş zamanlı miktar tayinleri başarıyla gerçekleştirilmiştir. Geliştirilen yöntemler, geleneksel tekniklere kıyasla basit, ekonomik ve verimli alternatifler sunmuştur.

Keywords

Atorvastatin , ezetimib , kemometri , PCR , PLS , spektrofotometri

References

1. Kengne, A.P., Jean-Baptiste, B., Pauline, L.N., Petya, K., Petar, A., Maryse, K., Omar, I., Khan, Z.M. (2024). Impact of single-pill combinations versus free-equivalent combinations on adherence and persistence in patients with hypertension and dyslipidemia: A systematic literature review and meta-analysis. Expert Review of Pharmacoeconomics & Outcomes Research, 24(7), 817-827. [CrossRef]
2. Weisser, B., Predel, H.G., Gillessen, A., Hacke, C., vor dem Esche, J., Rippin, G., Noetel, A., Randerath, O. (2020). Single pill regimen leads to better adherence and clinical outcome in daily practice in patients suffering from hypertension and/or dyslipidemia: Results of a meta-analysis. High Blood Pressure & Cardiovascular Prevention, 27(2), 157-164. [CrossRef]
3. Sen, S., Ganta, B., Rachel, V.N., Gogikar, S.K., Singh, V., Sonti, R., Dikundwar, A.G. (2024). Mapping advantages and challenges in analytical development for fixed dose combination products, a review. Journal of Pharmaceutical Sciences, 113(8), 2028-2043. [CrossRef]
4. Dinç, E., Baleanu, D., Ioele, G., De Luca, M., Ragno, G. (2008). Multivariate analysis of paracetamol, propiphenazone, caffeine and thiamine in quaternary mixtures by PCR, PLS and ANN calibrations applied on wavelet transform data. Journal of Pharmaceutical and Biomedical Analysis, 48(5), 1471-1475. [CrossRef]
5. Üstündağ, Ö., Dinç, E., Özdemir, N., Tilkan, M.G. (2015). Comparative application of PLS and PCR methods to simultaneous quantitative estimation and simultaneous dissolution test of zidovudine - lamivudine tablets. Acta Chimica Slovenica, 62(2), 437-444. [CrossRef]
6. Madan, J., Dwivedi, A.K., Singh, S. (2005). Estimation of antitubercular drugs combination in pharmaceutical formulations using multivariate calibration. Analytica Chimica Acta, 538(1), 345-353. [CrossRef]
7. Dinç, E., Üstündağ, Ö., Baleanu, D. (2010). Simultaneous chemometric determination of pyridoxine hydrochloride and isoniazid in tablets by multivariate regression methods. Drug Testing and Analysis, 2(8), 383-387. [CrossRef]
8. De Luca, M., Oliverio, F., Ioele, G., Ragno, G. (2009). Multivariate calibration techniques applied to derivative spectroscopy data for the analysis of pharmaceutical mixtures. Chemometrics and Intelligent Laboratory Systems, 96(1), 14-21. [CrossRef]
9. Ma, Y.B., Chan, P., Zhang, Y., Tomlinson, B., Liu, Z. (2019). Evaluating the efficacy and safety of atorvastatin + ezetimibe in a fixed-dose combination for the treatment of hypercholesterolemia. Expert Opin Pharmacother, 20(8), 917-928. [CrossRef]
10. Ferreira, A.M., Marques da Silva, P. (2017). Defining the place of ezetimibe/atorvastatin in the management of hyperlipidemia. American Journal of Cardiovascular Drugs, 17(3), 169-181. [CrossRef]
11. Qutab, S.S., Razzaq, S.N., Khan, I.U., Ashfaq, M., Shuja, Z.A. (2007). Simultaneous determination of atorvastatin calcium and ezetimibe in pharmaceutical formulations by liquid chromatography. Journal of Food and Drug Analysis, 15(2), 139-144. [CrossRef]
12. Seshachalam, U., Kothapally, C.B. (2008). Hplc analysis for simultaneous determination of atorvastatin and ezetimibe in pharmaceutical formulations. Journal of Liquid Chromatography and Related Technologies, 31(5), 714-721. [CrossRef]
13. Rajasekaran, A., Sasikumar, R., Dharuman, J. (2011). Simultaneous RP-HPLC method for the stress degradation studies of atorvastatin calcium and ezetimibe in multicomponent dosage form. Ars Pharmaceutica, 52(3), 12-18.
14. Talluri, M.V.N.K., Kalyankar, A., Ragampeta, S. (2012). Synchronized separation of atorvastatin - an antihyperlipidemic drug with antihypertensive, antidiabetic, antithrombotic drugs by rp-lc for determination in combined formulations. Journal of Pharmaceutical Analysis, 2(4), 285-292. [CrossRef]
15. Goel, A., Baboota, S., Sahni, J.K., Srinivas, K.S., Gupta, R.S., Gupta, A., Semwal, V.P., Ali, J. (2013). Development and validation of stability-indicating assay method by UPLC for a fixed dose combination of atorvastatin and ezetimibe. Journal of Chromatographic Science, 51(3), 222-228. [CrossRef]
16. Ashutosh Kumar, S., Debnath, M., Seshagiri Rao, J.V.L.N., Gowri Sankar, D. (2014). Stability indicating RP-HPLC analytical method development and validation for simultaneous estimation of atorvastatin and ezetimibe in bulk as well in pharmaceutical dosages form by using pda detector. Der Pharmacia Lettre, 6(5), 37-55.
17. Varghese, S.J., Ravi, T.K. (2014). Quantitative simultaneous determination of fenofibrate, atorvastatin, and ezetimibe in tablets using gradient high-performance column liquid chromatography and high-performance thin-layer chromatography. Journal of Liquid Chromatography and Related Technologies, 37(19), 2784-2799. [CrossRef]
18. Venkateswara Rao, B., Vidyadhara, S., Basaveswara Rao, M.V., Anusha, L. (2014). Validated RP-HPLC method for the simultaneous estimation of atorvastain and ezetimibe in pure and pharmaceutical formulations. Der Pharmacia Lettre, 6(4), 442-448.
19. Elzbieta, K., Ewa, M., Barbara, K.G., Krystyna, C., Elzbieta, W., Aleksander, P.M. (2015). Development of chromatographic method for determination of drugs reducing cholesterol level-statins and ezetimibe. Acta Poloniae Pharmaceutica-Drug Research, 72(3), 429-437.
20. Kumar, S.A., Debnath, M., Rao, J.V.L.N.S. (2015). New validated RP-HPLC analytical method for simultaneous estimation of atorvastatin and ezetimibe in bulk samples as well in tablet dosage forms by using pda detector. Current Drug Discovery Technologies, 11(4), 259-270. [CrossRef]
21. Raul, S.K., Aravelli, A.B., Jhansi, D. (2015). RP-HPLC method development and validation for the simultaneous estimation of atorvastatin and ezetimibe in pharmaceutical dosage form. Asian Journal of Pharmaceutical and Clinical Research, 8(2), 178-181.
22. Sree Janardhanan, V., Manavalan, R., Valliappan, K. (2016). Chemometric technique for the optimization of chromatographic system: Simultaneous HPLC determination of rosuvastatin, telmisartan, ezetimibe and atorvastatin used in combined cardiovascular therapy. Arabian Journal of Chemistry, 9, S1378-S1387. [CrossRef]
23. Patil, P.M., Bobade, A.S. (2016). Development and validation of stability indicating RP-HPLC for determination of atorvastatin calcium and ezetimibe in bulk and pharmaceutical dosage forms. International Journal of Pharmacy and Pharmaceutical Sciences, 8(6), 38-42.
24. Elbordiny, H.S., Elonsy, S.M., Daabees, H.G., Belal, T.S. (2024). Design of trio-colored validated HPLC method for synchronized multianalyte quantitation of four top selling antihyperlipidemic drugs in different fixed-dose combined tablets. Green Analytical Chemistry, 8, 100100. [CrossRef]
25. Nagavalli, D., Srinivas, B., Kalyan Chakravarthi, C. (2011). Simultaneous estimation of atorvastatin calcium, ezetimibe and fenofibrate in pure and combined tablet dosage form by UV spectrophotometry. International Journal of Pharmaceutical Sciences Review and Research, 8(2), 40-44.
26. Maher, H.M., Youssef, R.M., Hassan, E.M., El-Kimary, E.I., Barary, M.A. (2011). Enhanced spectrophotometric determination of two antihyperlipidemic mixtures containing ezetimibe in pharmaceutical preparations. Drug Testing and Analysis, 3(2), 97-105. [CrossRef]
27. Baldha, R.G., Patel Vandana, B., Bapna, M. (2009). Simultaneous spectrophotometric determination of atorvastatin calcium and ezetimibe in tablet dosage form. International Journal of ChemTech Research, 1(2), 233-236.
28. Abdelwahab, N.S., El-Zeiny, B.A., Tohamy, S.I. (2012). Two spectrophotometric methods for simultaneous determination of some antihyperlipidemic drugs. Journal of Pharmaceutical Analysis, 2(4), 279-284. [CrossRef]
29. Sonawane, S., Shirkhedkar, A., Fursule, R., Surana, S. (2007). Simultaneous spectrophotometric estimation of atorvastatin calcium and ezetimibe in tablets. Indian Journal of Pharmaceutical Sciences, 69(5), 683-684.
30. Baghdady, Y.Z., Al-Ghobashy, M.A., Abdel-Aleem, A.A.E., Weshahy, S.A. (2013). Spectrophotometric and tlc-densitometric methods for the simultaneous determination of ezetimibe and atorvastatin calcium. Journal of Advanced Research, 4(1), 51-59. [CrossRef]
31. Patel, V., Baldha, R., Patel, D. (2010). Simultaneous determination of atorvastatin calcium and ezetimib by ratio spectra derivative spectrophotometry and reverse phase-high performance liquid chromatography. Asian Journal of Chemistry, 22(4), 2511-2517.
32. Otto, M., Wegscheider, W. (1985). Spectrophotometric multicomponent analysis applied to trace metal determinations. Analytical Chemistry, 57(1), 63-69. [CrossRef]
33. Sebaiy, M.M., El-Adl, S.M., Nafea, A., Aljazzar, S.O., Elkaeed, E.B., Mattar, A.A., Elbaramawi, S.S. (2023). Different methods for resolving overlapping UV spectra of combination medicinal dose forms of ciprofloxacin and metronidazole. BMC Chem, 17(1), 137. [CrossRef]
34. Proma, M., Debarupa Dutta, C., Prithviraj, C., Bhupendra, S., Bhuyan, N.R. (2021). Different ultraviolet spectroscopic methods: a retrospective study on its application from the viewpoint of analytical chemistry. Asian Journal of Pharmaceutical and Clinical Research, 14(9), 1-11. [CrossRef]
35. Marbach, R., Heise, H.M. (1992). On the efficiency of algorithms for multivariate linear calibration used in analytical spectroscopy. TrAC Trends in Analytical Chemistry, 11(8), 270-275. [CrossRef]
36. Xu, L., Schechter, I. (1996). Wavelength selection for simultaneous spectroscopic analysis. Experimental and theoretical study. Analytical Chemistry, 68(14), 2392-2400. [CrossRef]
37. Wold, S., Kettaneh-Wold, N., Skagerberg, B. (1989). Nonlinear PLS modeling. Chemometrics and Intelligent Laboratory Systems, 7(1), 53-65. [CrossRef]
38. Olivieri, A.C. (2018). The partial least-squares model. In A. C. Olivieri (Ed.), Introduction to multivariate calibration: A practical approach (pp. 103-121). Cham: Springer International Publishing.
39. Jurado, J.M., Alcázar, A., Muñiz-Valencia, R., Ceballos-Magaña, S.G., Raposo, F. (2017). Some practical considerations for linearity assessment of calibration curves as function of concentration levels according to the fitness-for-purpose approach. Talanta, 172, 221-229. [CrossRef]
40. Olivieri, A.C. (2018). Principal component regression. In A. C. Olivieri (Ed.), Introduction to multivariate calibration: A practical approach (pp. 73-86). Cham: Springer International Publishing.
41. Dinç, E. (2007). Kemometri çok değişkenli kalibrasyon yöntemleri. Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi, 27(1), 61-92.
42. Dinç, E., Aktaş, A.H., Baleanu, D., Üstündaǧ, Ö. (2006). Simultaneous determination of tartrazine and allura red in commercial preparation by chemometric HPLC method. Journal of Food and Drug Analysis, 14(3), 284-291. [CrossRef]

SPECTROPHOTOMETRIC CO-ESTIMATION OF ATORVASTATIN AND EZETIMIBE IN A BINARY MIXTURE USING PRINCIPLE COMPONENT REGRESSION AND PARTIAL LEAST SQUARES REGRESSION MODELS

Year 2025, Volume: 49 Issue: 3, 827 - 837, 19.09.2025

Zehra Ceren Ertekin , Erdal Dinç

https://doi.org/10.33483/jfpau.1666211

Abstract

Objective: Fixed-dose formulations, such as combination of atorvastatin (AT) and ezetimibe (EZ), present analytical challenges due to overlapping spectral features in UV-Vis spectroscopy. Although traditional chromatographic methods are effective in these cases, they are not cost-efficient, and the required instrumentation is not easily accessible. This study aims to develop a simpler, cost-effective spectrophotometry-based approach for the simultaneous quantification of AT and EZ in fixed-dose formulations.
Material and Method: Principal component regression (PCR) and partial least squares (PLS) regression models were used in combination with UV-Vis spectroscopy. A calibration set of binary mixtures was prepared in the working range of 4–36 µg/ml for both drugs. PCR and PLS models were constructed using three latent variables. The developed methods were evaluated for accuracy, precision, and selectivity using laboratory-prepared samples. The applicability of the methods was demonstrated by analyzing commercial tablet samples.
Result and Discussion: Both models achieved high recovery rates (98–102.3%) and low relative standard deviations (<2.0%), confirming their accuracy and precision. Standard addition studies confirmed the selectivity of the methods. Then, the proposed PCR and PLS methods successfully quantified AT and EZ in commercial film-coated tablets without extensive sample preparation, offering a simple, cost-effective, and efficient alternative to conventional techniques.

Keywords

Atorvastatin , chemometrics , ezetimibe , PCR , PLS , spectrophotometry

References

1. Kengne, A.P., Jean-Baptiste, B., Pauline, L.N., Petya, K., Petar, A., Maryse, K., Omar, I., Khan, Z.M. (2024). Impact of single-pill combinations versus free-equivalent combinations on adherence and persistence in patients with hypertension and dyslipidemia: A systematic literature review and meta-analysis. Expert Review of Pharmacoeconomics & Outcomes Research, 24(7), 817-827. [CrossRef]
2. Weisser, B., Predel, H.G., Gillessen, A., Hacke, C., vor dem Esche, J., Rippin, G., Noetel, A., Randerath, O. (2020). Single pill regimen leads to better adherence and clinical outcome in daily practice in patients suffering from hypertension and/or dyslipidemia: Results of a meta-analysis. High Blood Pressure & Cardiovascular Prevention, 27(2), 157-164. [CrossRef]
3. Sen, S., Ganta, B., Rachel, V.N., Gogikar, S.K., Singh, V., Sonti, R., Dikundwar, A.G. (2024). Mapping advantages and challenges in analytical development for fixed dose combination products, a review. Journal of Pharmaceutical Sciences, 113(8), 2028-2043. [CrossRef]
4. Dinç, E., Baleanu, D., Ioele, G., De Luca, M., Ragno, G. (2008). Multivariate analysis of paracetamol, propiphenazone, caffeine and thiamine in quaternary mixtures by PCR, PLS and ANN calibrations applied on wavelet transform data. Journal of Pharmaceutical and Biomedical Analysis, 48(5), 1471-1475. [CrossRef]
5. Üstündağ, Ö., Dinç, E., Özdemir, N., Tilkan, M.G. (2015). Comparative application of PLS and PCR methods to simultaneous quantitative estimation and simultaneous dissolution test of zidovudine - lamivudine tablets. Acta Chimica Slovenica, 62(2), 437-444. [CrossRef]
6. Madan, J., Dwivedi, A.K., Singh, S. (2005). Estimation of antitubercular drugs combination in pharmaceutical formulations using multivariate calibration. Analytica Chimica Acta, 538(1), 345-353. [CrossRef]
7. Dinç, E., Üstündağ, Ö., Baleanu, D. (2010). Simultaneous chemometric determination of pyridoxine hydrochloride and isoniazid in tablets by multivariate regression methods. Drug Testing and Analysis, 2(8), 383-387. [CrossRef]
8. De Luca, M., Oliverio, F., Ioele, G., Ragno, G. (2009). Multivariate calibration techniques applied to derivative spectroscopy data for the analysis of pharmaceutical mixtures. Chemometrics and Intelligent Laboratory Systems, 96(1), 14-21. [CrossRef]
9. Ma, Y.B., Chan, P., Zhang, Y., Tomlinson, B., Liu, Z. (2019). Evaluating the efficacy and safety of atorvastatin + ezetimibe in a fixed-dose combination for the treatment of hypercholesterolemia. Expert Opin Pharmacother, 20(8), 917-928. [CrossRef]
10. Ferreira, A.M., Marques da Silva, P. (2017). Defining the place of ezetimibe/atorvastatin in the management of hyperlipidemia. American Journal of Cardiovascular Drugs, 17(3), 169-181. [CrossRef]
11. Qutab, S.S., Razzaq, S.N., Khan, I.U., Ashfaq, M., Shuja, Z.A. (2007). Simultaneous determination of atorvastatin calcium and ezetimibe in pharmaceutical formulations by liquid chromatography. Journal of Food and Drug Analysis, 15(2), 139-144. [CrossRef]
12. Seshachalam, U., Kothapally, C.B. (2008). Hplc analysis for simultaneous determination of atorvastatin and ezetimibe in pharmaceutical formulations. Journal of Liquid Chromatography and Related Technologies, 31(5), 714-721. [CrossRef]
13. Rajasekaran, A., Sasikumar, R., Dharuman, J. (2011). Simultaneous RP-HPLC method for the stress degradation studies of atorvastatin calcium and ezetimibe in multicomponent dosage form. Ars Pharmaceutica, 52(3), 12-18.
14. Talluri, M.V.N.K., Kalyankar, A., Ragampeta, S. (2012). Synchronized separation of atorvastatin - an antihyperlipidemic drug with antihypertensive, antidiabetic, antithrombotic drugs by rp-lc for determination in combined formulations. Journal of Pharmaceutical Analysis, 2(4), 285-292. [CrossRef]
15. Goel, A., Baboota, S., Sahni, J.K., Srinivas, K.S., Gupta, R.S., Gupta, A., Semwal, V.P., Ali, J. (2013). Development and validation of stability-indicating assay method by UPLC for a fixed dose combination of atorvastatin and ezetimibe. Journal of Chromatographic Science, 51(3), 222-228. [CrossRef]
16. Ashutosh Kumar, S., Debnath, M., Seshagiri Rao, J.V.L.N., Gowri Sankar, D. (2014). Stability indicating RP-HPLC analytical method development and validation for simultaneous estimation of atorvastatin and ezetimibe in bulk as well in pharmaceutical dosages form by using pda detector. Der Pharmacia Lettre, 6(5), 37-55.
17. Varghese, S.J., Ravi, T.K. (2014). Quantitative simultaneous determination of fenofibrate, atorvastatin, and ezetimibe in tablets using gradient high-performance column liquid chromatography and high-performance thin-layer chromatography. Journal of Liquid Chromatography and Related Technologies, 37(19), 2784-2799. [CrossRef]
18. Venkateswara Rao, B., Vidyadhara, S., Basaveswara Rao, M.V., Anusha, L. (2014). Validated RP-HPLC method for the simultaneous estimation of atorvastain and ezetimibe in pure and pharmaceutical formulations. Der Pharmacia Lettre, 6(4), 442-448.
19. Elzbieta, K., Ewa, M., Barbara, K.G., Krystyna, C., Elzbieta, W., Aleksander, P.M. (2015). Development of chromatographic method for determination of drugs reducing cholesterol level-statins and ezetimibe. Acta Poloniae Pharmaceutica-Drug Research, 72(3), 429-437.
20. Kumar, S.A., Debnath, M., Rao, J.V.L.N.S. (2015). New validated RP-HPLC analytical method for simultaneous estimation of atorvastatin and ezetimibe in bulk samples as well in tablet dosage forms by using pda detector. Current Drug Discovery Technologies, 11(4), 259-270. [CrossRef]
21. Raul, S.K., Aravelli, A.B., Jhansi, D. (2015). RP-HPLC method development and validation for the simultaneous estimation of atorvastatin and ezetimibe in pharmaceutical dosage form. Asian Journal of Pharmaceutical and Clinical Research, 8(2), 178-181.
22. Sree Janardhanan, V., Manavalan, R., Valliappan, K. (2016). Chemometric technique for the optimization of chromatographic system: Simultaneous HPLC determination of rosuvastatin, telmisartan, ezetimibe and atorvastatin used in combined cardiovascular therapy. Arabian Journal of Chemistry, 9, S1378-S1387. [CrossRef]
23. Patil, P.M., Bobade, A.S. (2016). Development and validation of stability indicating RP-HPLC for determination of atorvastatin calcium and ezetimibe in bulk and pharmaceutical dosage forms. International Journal of Pharmacy and Pharmaceutical Sciences, 8(6), 38-42.
24. Elbordiny, H.S., Elonsy, S.M., Daabees, H.G., Belal, T.S. (2024). Design of trio-colored validated HPLC method for synchronized multianalyte quantitation of four top selling antihyperlipidemic drugs in different fixed-dose combined tablets. Green Analytical Chemistry, 8, 100100. [CrossRef]
25. Nagavalli, D., Srinivas, B., Kalyan Chakravarthi, C. (2011). Simultaneous estimation of atorvastatin calcium, ezetimibe and fenofibrate in pure and combined tablet dosage form by UV spectrophotometry. International Journal of Pharmaceutical Sciences Review and Research, 8(2), 40-44.
26. Maher, H.M., Youssef, R.M., Hassan, E.M., El-Kimary, E.I., Barary, M.A. (2011). Enhanced spectrophotometric determination of two antihyperlipidemic mixtures containing ezetimibe in pharmaceutical preparations. Drug Testing and Analysis, 3(2), 97-105. [CrossRef]
27. Baldha, R.G., Patel Vandana, B., Bapna, M. (2009). Simultaneous spectrophotometric determination of atorvastatin calcium and ezetimibe in tablet dosage form. International Journal of ChemTech Research, 1(2), 233-236.
28. Abdelwahab, N.S., El-Zeiny, B.A., Tohamy, S.I. (2012). Two spectrophotometric methods for simultaneous determination of some antihyperlipidemic drugs. Journal of Pharmaceutical Analysis, 2(4), 279-284. [CrossRef]
29. Sonawane, S., Shirkhedkar, A., Fursule, R., Surana, S. (2007). Simultaneous spectrophotometric estimation of atorvastatin calcium and ezetimibe in tablets. Indian Journal of Pharmaceutical Sciences, 69(5), 683-684.
30. Baghdady, Y.Z., Al-Ghobashy, M.A., Abdel-Aleem, A.A.E., Weshahy, S.A. (2013). Spectrophotometric and tlc-densitometric methods for the simultaneous determination of ezetimibe and atorvastatin calcium. Journal of Advanced Research, 4(1), 51-59. [CrossRef]
31. Patel, V., Baldha, R., Patel, D. (2010). Simultaneous determination of atorvastatin calcium and ezetimib by ratio spectra derivative spectrophotometry and reverse phase-high performance liquid chromatography. Asian Journal of Chemistry, 22(4), 2511-2517.
32. Otto, M., Wegscheider, W. (1985). Spectrophotometric multicomponent analysis applied to trace metal determinations. Analytical Chemistry, 57(1), 63-69. [CrossRef]
33. Sebaiy, M.M., El-Adl, S.M., Nafea, A., Aljazzar, S.O., Elkaeed, E.B., Mattar, A.A., Elbaramawi, S.S. (2023). Different methods for resolving overlapping UV spectra of combination medicinal dose forms of ciprofloxacin and metronidazole. BMC Chem, 17(1), 137. [CrossRef]
34. Proma, M., Debarupa Dutta, C., Prithviraj, C., Bhupendra, S., Bhuyan, N.R. (2021). Different ultraviolet spectroscopic methods: a retrospective study on its application from the viewpoint of analytical chemistry. Asian Journal of Pharmaceutical and Clinical Research, 14(9), 1-11. [CrossRef]
35. Marbach, R., Heise, H.M. (1992). On the efficiency of algorithms for multivariate linear calibration used in analytical spectroscopy. TrAC Trends in Analytical Chemistry, 11(8), 270-275. [CrossRef]
36. Xu, L., Schechter, I. (1996). Wavelength selection for simultaneous spectroscopic analysis. Experimental and theoretical study. Analytical Chemistry, 68(14), 2392-2400. [CrossRef]
37. Wold, S., Kettaneh-Wold, N., Skagerberg, B. (1989). Nonlinear PLS modeling. Chemometrics and Intelligent Laboratory Systems, 7(1), 53-65. [CrossRef]
38. Olivieri, A.C. (2018). The partial least-squares model. In A. C. Olivieri (Ed.), Introduction to multivariate calibration: A practical approach (pp. 103-121). Cham: Springer International Publishing.
39. Jurado, J.M., Alcázar, A., Muñiz-Valencia, R., Ceballos-Magaña, S.G., Raposo, F. (2017). Some practical considerations for linearity assessment of calibration curves as function of concentration levels according to the fitness-for-purpose approach. Talanta, 172, 221-229. [CrossRef]
40. Olivieri, A.C. (2018). Principal component regression. In A. C. Olivieri (Ed.), Introduction to multivariate calibration: A practical approach (pp. 73-86). Cham: Springer International Publishing.
41. Dinç, E. (2007). Kemometri çok değişkenli kalibrasyon yöntemleri. Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi, 27(1), 61-92.
42. Dinç, E., Aktaş, A.H., Baleanu, D., Üstündaǧ, Ö. (2006). Simultaneous determination of tartrazine and allura red in commercial preparation by chemometric HPLC method. Journal of Food and Drug Analysis, 14(3), 284-291. [CrossRef]

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Details

Primary Language	English
Subjects	Pharmaceutical Analytical Chemistry
Journal Section	Research Article
Authors	Zehra Ceren Ertekin 0000-0002-1549-6024 Erdal Dinç 0000-0001-6326-1441
Early Pub Date	August 13, 2025
Publication Date	September 19, 2025
Submission Date	March 26, 2025
Acceptance Date	May 12, 2025
Published in Issue	Year 2025 Volume: 49 Issue: 3

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APA	Ertekin, Z. C., & Dinç, E. (2025). SPECTROPHOTOMETRIC CO-ESTIMATION OF ATORVASTATIN AND EZETIMIBE IN A BINARY MIXTURE USING PRINCIPLE COMPONENT REGRESSION AND PARTIAL LEAST SQUARES REGRESSION MODELS. Journal of Faculty of Pharmacy of Ankara University, 49(3), 827-837. https://doi.org/10.33483/jfpau.1666211
AMA	Ertekin ZC, Dinç E. SPECTROPHOTOMETRIC CO-ESTIMATION OF ATORVASTATIN AND EZETIMIBE IN A BINARY MIXTURE USING PRINCIPLE COMPONENT REGRESSION AND PARTIAL LEAST SQUARES REGRESSION MODELS. J. Fac. Pharm. Ankara. September 2025;49(3):827-837. doi:10.33483/jfpau.1666211
Chicago	Ertekin, Zehra Ceren, and Erdal Dinç. “SPECTROPHOTOMETRIC CO-ESTIMATION OF ATORVASTATIN AND EZETIMIBE IN A BINARY MIXTURE USING PRINCIPLE COMPONENT REGRESSION AND PARTIAL LEAST SQUARES REGRESSION MODELS”. Journal of Faculty of Pharmacy of Ankara University 49, no. 3 (September 2025): 827-37. https://doi.org/10.33483/jfpau.1666211.
EndNote	Ertekin ZC, Dinç E (September 1, 2025) SPECTROPHOTOMETRIC CO-ESTIMATION OF ATORVASTATIN AND EZETIMIBE IN A BINARY MIXTURE USING PRINCIPLE COMPONENT REGRESSION AND PARTIAL LEAST SQUARES REGRESSION MODELS. Journal of Faculty of Pharmacy of Ankara University 49 3 827–837.
IEEE	Z. C. Ertekin and E. Dinç, “SPECTROPHOTOMETRIC CO-ESTIMATION OF ATORVASTATIN AND EZETIMIBE IN A BINARY MIXTURE USING PRINCIPLE COMPONENT REGRESSION AND PARTIAL LEAST SQUARES REGRESSION MODELS”, J. Fac. Pharm. Ankara, vol. 49, no. 3, pp. 827–837, 2025, doi: 10.33483/jfpau.1666211.
ISNAD	Ertekin, Zehra Ceren - Dinç, Erdal. “SPECTROPHOTOMETRIC CO-ESTIMATION OF ATORVASTATIN AND EZETIMIBE IN A BINARY MIXTURE USING PRINCIPLE COMPONENT REGRESSION AND PARTIAL LEAST SQUARES REGRESSION MODELS”. Journal of Faculty of Pharmacy of Ankara University 49/3 (September2025), 827-837. https://doi.org/10.33483/jfpau.1666211.
JAMA	Ertekin ZC, Dinç E. SPECTROPHOTOMETRIC CO-ESTIMATION OF ATORVASTATIN AND EZETIMIBE IN A BINARY MIXTURE USING PRINCIPLE COMPONENT REGRESSION AND PARTIAL LEAST SQUARES REGRESSION MODELS. J. Fac. Pharm. Ankara. 2025;49:827–837.
MLA	Ertekin, Zehra Ceren and Erdal Dinç. “SPECTROPHOTOMETRIC CO-ESTIMATION OF ATORVASTATIN AND EZETIMIBE IN A BINARY MIXTURE USING PRINCIPLE COMPONENT REGRESSION AND PARTIAL LEAST SQUARES REGRESSION MODELS”. Journal of Faculty of Pharmacy of Ankara University, vol. 49, no. 3, 2025, pp. 827-3, doi:10.33483/jfpau.1666211.
Vancouver	Ertekin ZC, Dinç E. SPECTROPHOTOMETRIC CO-ESTIMATION OF ATORVASTATIN AND EZETIMIBE IN A BINARY MIXTURE USING PRINCIPLE COMPONENT REGRESSION AND PARTIAL LEAST SQUARES REGRESSION MODELS. J. Fac. Pharm. Ankara. 2025;49(3):827-3.

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The Journal of Faculty of Pharmacy of Ankara University is an international medium, an open access, peer-reviewed journal for the publication of original research reports, reviews and short communications in English or Turkish on relevant developments in pharmaceutical sciences., Proceeding of scientific meetings may be published as special issues of supplements to the journal. Additionally, it contains previous and forthcoming national and international scientific meetings with social activities in pharmaceutical areas.