Development and Validation of A Green HPLC Method for Estimation of Empagliflozin in Pharmaceutical Products

İbrahim Bulduk; Erten Akbel; Serdar Güngör; Süleyman Gökce

doi:10.47495/okufbed.1626492

Araştırma Makalesi

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Kaynak Göster

Development and Validation of A Green HPLC Method for Estimation of Empagliflozin in Pharmaceutical Products

Yıl 2025, Cilt: 8 Sayı: 3, 1333 - 1352, 16.06.2025

İbrahim Bulduk , Erten Akbel , Serdar Güngör , Süleyman Gökce

https://doi.org/10.47495/okufbed.1626492

Öz

In this study, two different chromatographic methods were developed for the quantification of empagliflozin in pharmaceutical products. The first was the classical method using acetonitrile as an organic modifier in the mobile phase and the second was the green method using ethanol as an organic modifier in the mobile phase. In the classical method, an Extend C18 column (250 x 4.6 mm, 5 µm) was used and the temperature was kept constant at 30 °C. The mobile phase was the formic acid solution (0.1% in ultrapure water) and acetonitrile (55/45, v/v), and isocratic elution was applied. The flow rate of the mobile phase was 1.0 mL min-1 and the injection volume was 10 µL. Detection was performed using a UV detector at 223 nm. In the green method, ethanol was used as an organic modifier. The only difference between these methods was the organic modifier. All other conditions of the methods were identical. Both chromatographic methods were validated according to ICH guidelines for various parameters such as selectivity, linearity, accuracy, precision, limit of detection and quantification, and robustness. The coefficients of determination of the chromatographic methods were greater than 0.999 in the concentration range of 5-30 mg mL-1 glyclazide. The developed chromatographic methods were applied to pharmaceutical formulations. Comparisons of the results obtained in terms of means were made using the Student (t) test and in terms of standard deviations using the Fischer (F) test. There was no significant difference between these methods. The environmental impact of both methods was evaluated using AGREE and GAPI software, confirming their sustainability. These validated methods provide reliable and environmentally friendly approaches for the quantitative analysis of EPG in tablet formulations, supporting safer and more sustainable laboratory practices in pharmaceutical analysis. For the quantitative analysis of EPG in pharmaceutical products, the new approach can be viewed as an affordable and ecologically responsible alternative to the methods now in use.

Anahtar Kelimeler

Green analytical method, empagliflozin, chromatographic method

Kaynakça

Abbas NS., Derayea SM., Omar MA., Saleh GA. Innovative TLC-densitometric method with fluorescent detection for simultaneous determination of ternary anti-diabetic mixture in pharmaceutical formulations and human plasma. Microchem. J. 2021; 165: 106131–106143.
Abdel-Ghany MF., Abdel-Aziz O., Ayad MF., Tadros MM. New LC–UV methods for the pharmaceutical analysis of novel anti-diabetic combinations. Acta Chromatogr 2017; 29: 448–452.
Abdel-Ghany MF., Ayad MF., Tadros MM. Liquid chromatographic and spectrofluorimetric assays of empagliflozin: Applied to degradation kinetic study and content uniformity testing. Luminescence 2018; 33: 919–932.
Ayoub BM. Development and validation of simple spectrophotometric and chemometric methods for simultaneous determination of empagliflozin and metformin: Applied to recently approved pharmaceutical formulation. Spectrochim Acta A Mol Biomol Spectrosc 2016; 168: 118-122.
Ayoub BM. Green pharmaceutical analysis of drugs coformulated with highly different concentrations using spiking and manipulation of their ratio spectra. JAOAC Int. 2017; 100(4): 985-991.
Ayoub BM., Mowaka S. LC–MS/MS determination of empagliflozin and metformin. J. Chromatogr. Sci. 2017; 55: 742–747.
Badragheh S., Zeeb M., Olyai MRTB. Silica-coated magnetic iron oxide functionalized with hydrophobic polymeric ionic liquid: A promising nanoscale sorbent for the simultaneous extraction of antidiabetic drugs from human plasma prior to their quantitation by HPLC. RSC Adv. 2018; 8: 30550–30561.
Burin SL., Lourenço RL., Doneda M., Müller EI., Paula FR., Adams AIH. Development of an HPLC-UV method to assay empagliflozin tablets and ıdentification of the major photoproduct by quadrupole time-of-flight mass spectrometry. J. Chromatogr. Sci. 2021; 59: 526–535.
Capello C., Fischer U., Hungerbühler K. What is a green solvent? A comprehensive framework for the environmental assessment of solvents. Green Chem. 2007 9: 927–934.
Center for Drug Evaluation and Research (CDER). Reviewer Guidance: Validation of Chromatographic Methods;1994.
Dias BCL., Fachi MM., de Campos ML., Degaut FLD., Peccinini RG., Pontarolo R. A new HPLC–MS/MS method for the simultaneous quantification of SGLT2 inhibitors and metformin in plasma and its application to a pharmacokinetic study in healthy volunteers. Biomed. Chromatogr. 2019; 33: e4663.
El-Kafrawy DS., El-Shoubashy OH., Issa AE., Beltagy YA. Green chromatographic methods for simultaneous micro determination of empagliflozin, linagliptin with metformin and its pharmacopoeial impurities in pure form and triple combination tablets: A comparative study. Sust. Chem. Pharm. 2022; 25: 100560–100572.
Elnadi S., Abdalsabour S., Abdalghany MF., Trabik YA. Stability indicating RP-HPLC and spectrophotometric methods for determination of gliflozins in their mixture with metformin. J. Iranian Chem. Soc. 2022; 19: 1723–1735.
Gałuszka A., Migaszewski ZM., Konieczka P., Namieśnik J. Analytical eco-scale for assessing the greenness of analytical procedures. TrAC Trends Anal. Chem. 2012; 37: 61–72.
Gollu G., Gummadi S. A rapid LC-PDA method for the simultaneous quantification of metformin, empagliflozin, and linagliptin in the pharmaceutical dosage form. Ann. Pharm. Françaises 2022; 80: 48–58.
Görög S. The changing face of pharmaceutical analysis. TrAC Trends Anal. Chem. 2007; 26: 12–17.
Hassib ST., Taha EA., Elkady EF., Barakat GH. Validated liquid chromatographic method for the determination of (canagliflozin, dapagliflozin or empagliflozin) and metformin in the presence of (1-cyanoguanidine). J. Chromatogr. Sci. 2019; 57: 697–707. https://go.drugbank.com/drugs/DB09038
ICH Harmonised Tripartite Guideline Impurities: Guideline for residual solvents Q3C (R5). Curr. Step 2005; 4: 509.
Keith LH., Gron LU., Young JL. Green analytical methodologies. Chem. Rev. 2007; 107: 2695–2708.
Mabrouk MM., Soliman SM., El-Agizy HM., Mansour FR. Ultrasound-assisted dispersive liquid–liquid microextraction for determination of three gliflozins in human plasma by HPLC/DAD. J. Chromatogr. B 2020; 1136: 121932.
Manoel JW., Primieri GB., Bueno LM., Wingert NR., Volpato NM., Garcia CV., Steppe M. The application of quality by design in the development of the liquid chromatography method to determine empagliflozin in the presence of its organic impurities. RSC Adv. 2020; 10: 7313–7320.
Marie AA., Salim MM., Kamal AH., Hammad SF., Elkhoudary MM. Analytical quality by design based on design space in reversed-phase-high performance liquid chromatography analysis for simultaneous estimation of metformin, linagliptin, and empagliflozin. R. Soc. Open Sci. 2022; 9: 220215–220228.
Miyabe K., Takeuchi S., Tezuka Y. Adsorption characteristics in reversed-phase liquid chromatography using ethanol/water mixed solvent. Adsorption 1999; 5: 15–24.
Mohamed HM. Green, environment-friendly, analytical tools give insights in pharmaceuticals and cosmetics analysis. TrAC Trends Anal. Chem. 2015; 66: 176–192.
Moussa BA., Mahrouse MA., Fawzy MG. Application of experimental design in HPLC method optimization and robustness for the simultaneous determination of canagliflozin, empagliflozin, linagliptin, and metformin in the tablet. Biomed. Chromatogr. 2021; 35: e5155–e5166.
Padmaja N., Veerabhadram G. Development and validation of analytical method for Simultaneous estimation of Empagliflozin and Linagliptin in bulk drugs and combined dosage forms using UV-visible spectroscopy. Pharm Lett. 2015; 7(12): 306-312.
Pandya PA., Shah PA., Shrivastav PS. Separation of achiral anti-diabetic drugs using sub/supercritical fluid chromatography with a polysaccharide stationary phase: Thermodynamic considerations and molecular docking study. J. Pharm. Biomed. Anal. 2020; 189: 113452–113464.
Patel IM., Chhalotiya UK., Jani HD., Kansara D., Shah DA. Densitometric simultaneous estimation of the combination of empagliflozin, linagliptin and metformin hydrochloride used in the treatment of type 2 diabetes mellitus. J. Planar Chromatogr. 2022; 33: 109–118.
Pena-Pereira F., Wojnowski W., Tobiszewski M. AGREE—Analytical greenness metric approachv and software. Anal Chem. 2020; 92: 10076–82.
Płotka J., Tobiszewski M., Sulej AM., Kupska M., Górecki T., Namieśnik J. Green chromatography. J. Chromatogr. A 2013; 1307: 1–20.
Płotka-Wasylka J. A new tool for the evaluation of the analytical procedure: Green analytical procedure index. Talanta 2018; 181: 204–209.
Ribeiro RL., Bottoli CB., Collins KE., Collins CH. Reevaluation of ethanol as organic modifier for use in HPLS-RP mobile phases. J. Braz. Chem. Soc. 2004; 15: 300–306.
Shaaban H., Górecki T. Current trends in green liquid chromatography for the analysis of pharmaceutically active compounds in the environmental water compartments. Talanta 2015; 132: 739–752.
Shah PA., Shrivastav PS., George A. Mixed-mode solid phase extraction combined with LC-MS/MS for determination of empagliflozin and linagliptin in human plasma. Microchem. J. 2019a; 145: 523–531.
Shah PA., Shrivastav PS., Sharma V., Yadav MS. Challenges in simultaneous extraction and chromatographic separation of metformin and three SGLT-2 inhibitors in human plasma using LC–MS/MS. J. Pharm. Biomed. Anal. 2019b; 175: 112790–112799.
Sharif S., Bashir R., Adnan A., Mansoor S., Ahmad I., Ch AR., Tahir MS. Stability indicating, pH and pKa dependent HPLC–DAD method for the simultaneous determination of weakly ıonizable empagliflozin, dapagliflozin, and canagliflozin in pharmaceutical formulations. Chromatographia 2020; 83: 1453–1465
Sheldon RA. Fundamentals of green chemistry: Efficiency in reaction design. Chem. Soc. Rev. 2012; 41: 1437–1451.
Shen Y., Chen B., van Beek TA. Alternative solvents can make preparative liquid chromatography greener. Green Chem. 2015; 17: 4073–4081.
Snyder LR., Kirkland JJ., Dolan JW. Introduction to modern liquid chromatography; John Wiley & Sons, Inc.: Hoboken, NJ, USA: 2009; ISBN 978-0-470-50818-3.
Thakor NS., Amrutkar SV., Chaudhari PD. Simultaneous estimation of empagliflozin and metformin by high-performance thin-layer chromatography using quality-by-design approach. J. Planar Chromatogr. 2019; 32: 295–307.
Tobiszewski M., Mechlińska A., Namieśnik J. Green analytical chemistry—Theory and practice. Chem. Soc. Rev. 2010; 39: 2869–2878.
Tobiszewski M., Marć M., Gałuszka A., Namieśnik J. Green chemistry metrics with special reference to green analytical chemistry. Molecules 2015; 20: 10928–10946.
Tobiszewski M. Metrics for green analytical chemistry. Anal. Methods 2016; 8: 2993–2999.
Validation of analytical procedures: text and methodology Q2(R1)-ICH harmonized tripartite guideline. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use; 2005
Van der Aart-van AB., Wessels AMA., Heerspink HJ., Touw DJ. Simple, fast and robust LC-MS/MS method for the simultaneous quantification of canagliflozin, dapagliflozin and empagliflozin in human plasma and urine. J. Chromatogr. B 2020; 1152: 122257.
Welch CJ., Wu N., Biba M., Hartman R., Brkovic T., Gong X., Helmy R., Schafer W., Cuff J., Pirzada Z. Greening analytical chromatography. TrAC Trends Anal. Chem. 2010; 29: 667–680.
Wittich CM., Beckman TJ. Mayo clinic ınternal medicine board review, 12th ed.; Oxford University Press: Oxford, UK 2020; 168–225.

Farmasötik Ürünlerde Empagliflozin Tahmini İçin Yeşil bir HPLC Yönteminin Geliştirilmesi ve Validasyonu

Yıl 2025, Cilt: 8 Sayı: 3, 1333 - 1352, 16.06.2025

İbrahim Bulduk , Erten Akbel , Serdar Güngör , Süleyman Gökce

https://doi.org/10.47495/okufbed.1626492

Öz

Bu çalışmada, empagliflozinin farmasötik ürünlerdeki miktar tayini için iki farklı kromatografik yöntem geliştirilmiştir. Bunlardan ilki mobil fazda organik değiştirici olarak asetonitril kullanılan klasik yöntem, ikincisi ise mobil fazda organik değiştirici olarak etanol kullanılan yeşil yöntemdir. Klasik yöntemde Extend C18 kolon (250 x 4,6 mm, 5 µm) kullanılmış ve sıcaklık 30 °C'de sabit tutulmuştur. Mobil faz formik asit çözeltisi (ultra saf suda %0,1) ve asetonitril (55/45, v/v) idi ve izokratik elüsyon uygulandı. Mobil fazın akış hızı 1,0 mL dk-1 ve enjeksiyon hacmi 10 µL idi. Tespit 223 nm'de bir UV dedektörü kullanılarak gerçekleştirilmiştir. Yeşil yöntemde organik değiştirici olarak etanol kullanılmıştır. Bu yöntemler arasındaki tek fark organik değiştiriciydi. Yöntemlerin diğer tüm koşulları aynıydı. Her iki kromatografik yöntem de seçicilik, doğrusallık, doğruluk, kesinlik, saptama ve miktar belirleme limiti ve sağlamlık gibi çeşitli parametreler açısından ICH kılavuzlarına göre doğrulanmıştır. Kromatografik yöntemlerin tayin katsayıları 5-30 mg mL-1 gliklazid konsantrasyon aralığında 0.999'dan büyüktü. Geliştirilen kromatografik yöntemler farmasötik formülasyonlara uygulanmıştır. Elde edilen sonuçların ortalamalar açısından karşılaştırmaları Student (t) testi, standart sapmalar açısından karşılaştırmaları ise Fischer (F) testi kullanılarak yapılmıştır. Bu yöntemler arasında anlamlı bir fark bulunmamıştır. Her iki yöntemin çevresel etkisi AGREE ve GAPI yazılımları kullanılarak değerlendirilmiş ve sürdürülebilirlikleri teyit edilmiştir. Bu doğrulanmış metotlar, tablet formülasyonlarında EPG'nin kantitatif analizi için güvenilir ve çevre dostu yaklaşımlar sunarak farmasötik analizlerde daha güvenli ve sürdürülebilir laboratuvar uygulamalarını desteklemektedir. Farmasötik ürünlerdeki EPG'nin kantitatif analizi için yeni yaklaşım, şu anda kullanılan yöntemlere ekonomik ve ekolojik açıdan sorumlu bir alternatif olarak görülebilir.

Anahtar Kelimeler

Yeşil analitik metod, empagliflozin, kromatografik metod

Kaynakça

Abbas NS., Derayea SM., Omar MA., Saleh GA. Innovative TLC-densitometric method with fluorescent detection for simultaneous determination of ternary anti-diabetic mixture in pharmaceutical formulations and human plasma. Microchem. J. 2021; 165: 106131–106143.
Abdel-Ghany MF., Abdel-Aziz O., Ayad MF., Tadros MM. New LC–UV methods for the pharmaceutical analysis of novel anti-diabetic combinations. Acta Chromatogr 2017; 29: 448–452.
Abdel-Ghany MF., Ayad MF., Tadros MM. Liquid chromatographic and spectrofluorimetric assays of empagliflozin: Applied to degradation kinetic study and content uniformity testing. Luminescence 2018; 33: 919–932.
Ayoub BM. Development and validation of simple spectrophotometric and chemometric methods for simultaneous determination of empagliflozin and metformin: Applied to recently approved pharmaceutical formulation. Spectrochim Acta A Mol Biomol Spectrosc 2016; 168: 118-122.
Ayoub BM. Green pharmaceutical analysis of drugs coformulated with highly different concentrations using spiking and manipulation of their ratio spectra. JAOAC Int. 2017; 100(4): 985-991.
Ayoub BM., Mowaka S. LC–MS/MS determination of empagliflozin and metformin. J. Chromatogr. Sci. 2017; 55: 742–747.
Badragheh S., Zeeb M., Olyai MRTB. Silica-coated magnetic iron oxide functionalized with hydrophobic polymeric ionic liquid: A promising nanoscale sorbent for the simultaneous extraction of antidiabetic drugs from human plasma prior to their quantitation by HPLC. RSC Adv. 2018; 8: 30550–30561.
Burin SL., Lourenço RL., Doneda M., Müller EI., Paula FR., Adams AIH. Development of an HPLC-UV method to assay empagliflozin tablets and ıdentification of the major photoproduct by quadrupole time-of-flight mass spectrometry. J. Chromatogr. Sci. 2021; 59: 526–535.
Capello C., Fischer U., Hungerbühler K. What is a green solvent? A comprehensive framework for the environmental assessment of solvents. Green Chem. 2007 9: 927–934.
Center for Drug Evaluation and Research (CDER). Reviewer Guidance: Validation of Chromatographic Methods;1994.
Dias BCL., Fachi MM., de Campos ML., Degaut FLD., Peccinini RG., Pontarolo R. A new HPLC–MS/MS method for the simultaneous quantification of SGLT2 inhibitors and metformin in plasma and its application to a pharmacokinetic study in healthy volunteers. Biomed. Chromatogr. 2019; 33: e4663.
El-Kafrawy DS., El-Shoubashy OH., Issa AE., Beltagy YA. Green chromatographic methods for simultaneous micro determination of empagliflozin, linagliptin with metformin and its pharmacopoeial impurities in pure form and triple combination tablets: A comparative study. Sust. Chem. Pharm. 2022; 25: 100560–100572.
Elnadi S., Abdalsabour S., Abdalghany MF., Trabik YA. Stability indicating RP-HPLC and spectrophotometric methods for determination of gliflozins in their mixture with metformin. J. Iranian Chem. Soc. 2022; 19: 1723–1735.
Gałuszka A., Migaszewski ZM., Konieczka P., Namieśnik J. Analytical eco-scale for assessing the greenness of analytical procedures. TrAC Trends Anal. Chem. 2012; 37: 61–72.
Gollu G., Gummadi S. A rapid LC-PDA method for the simultaneous quantification of metformin, empagliflozin, and linagliptin in the pharmaceutical dosage form. Ann. Pharm. Françaises 2022; 80: 48–58.
Görög S. The changing face of pharmaceutical analysis. TrAC Trends Anal. Chem. 2007; 26: 12–17.
Hassib ST., Taha EA., Elkady EF., Barakat GH. Validated liquid chromatographic method for the determination of (canagliflozin, dapagliflozin or empagliflozin) and metformin in the presence of (1-cyanoguanidine). J. Chromatogr. Sci. 2019; 57: 697–707. https://go.drugbank.com/drugs/DB09038
ICH Harmonised Tripartite Guideline Impurities: Guideline for residual solvents Q3C (R5). Curr. Step 2005; 4: 509.
Keith LH., Gron LU., Young JL. Green analytical methodologies. Chem. Rev. 2007; 107: 2695–2708.
Mabrouk MM., Soliman SM., El-Agizy HM., Mansour FR. Ultrasound-assisted dispersive liquid–liquid microextraction for determination of three gliflozins in human plasma by HPLC/DAD. J. Chromatogr. B 2020; 1136: 121932.
Manoel JW., Primieri GB., Bueno LM., Wingert NR., Volpato NM., Garcia CV., Steppe M. The application of quality by design in the development of the liquid chromatography method to determine empagliflozin in the presence of its organic impurities. RSC Adv. 2020; 10: 7313–7320.
Marie AA., Salim MM., Kamal AH., Hammad SF., Elkhoudary MM. Analytical quality by design based on design space in reversed-phase-high performance liquid chromatography analysis for simultaneous estimation of metformin, linagliptin, and empagliflozin. R. Soc. Open Sci. 2022; 9: 220215–220228.
Miyabe K., Takeuchi S., Tezuka Y. Adsorption characteristics in reversed-phase liquid chromatography using ethanol/water mixed solvent. Adsorption 1999; 5: 15–24.
Mohamed HM. Green, environment-friendly, analytical tools give insights in pharmaceuticals and cosmetics analysis. TrAC Trends Anal. Chem. 2015; 66: 176–192.
Moussa BA., Mahrouse MA., Fawzy MG. Application of experimental design in HPLC method optimization and robustness for the simultaneous determination of canagliflozin, empagliflozin, linagliptin, and metformin in the tablet. Biomed. Chromatogr. 2021; 35: e5155–e5166.
Padmaja N., Veerabhadram G. Development and validation of analytical method for Simultaneous estimation of Empagliflozin and Linagliptin in bulk drugs and combined dosage forms using UV-visible spectroscopy. Pharm Lett. 2015; 7(12): 306-312.
Pandya PA., Shah PA., Shrivastav PS. Separation of achiral anti-diabetic drugs using sub/supercritical fluid chromatography with a polysaccharide stationary phase: Thermodynamic considerations and molecular docking study. J. Pharm. Biomed. Anal. 2020; 189: 113452–113464.
Patel IM., Chhalotiya UK., Jani HD., Kansara D., Shah DA. Densitometric simultaneous estimation of the combination of empagliflozin, linagliptin and metformin hydrochloride used in the treatment of type 2 diabetes mellitus. J. Planar Chromatogr. 2022; 33: 109–118.
Pena-Pereira F., Wojnowski W., Tobiszewski M. AGREE—Analytical greenness metric approachv and software. Anal Chem. 2020; 92: 10076–82.
Płotka J., Tobiszewski M., Sulej AM., Kupska M., Górecki T., Namieśnik J. Green chromatography. J. Chromatogr. A 2013; 1307: 1–20.
Płotka-Wasylka J. A new tool for the evaluation of the analytical procedure: Green analytical procedure index. Talanta 2018; 181: 204–209.
Ribeiro RL., Bottoli CB., Collins KE., Collins CH. Reevaluation of ethanol as organic modifier for use in HPLS-RP mobile phases. J. Braz. Chem. Soc. 2004; 15: 300–306.
Shaaban H., Górecki T. Current trends in green liquid chromatography for the analysis of pharmaceutically active compounds in the environmental water compartments. Talanta 2015; 132: 739–752.
Shah PA., Shrivastav PS., George A. Mixed-mode solid phase extraction combined with LC-MS/MS for determination of empagliflozin and linagliptin in human plasma. Microchem. J. 2019a; 145: 523–531.
Shah PA., Shrivastav PS., Sharma V., Yadav MS. Challenges in simultaneous extraction and chromatographic separation of metformin and three SGLT-2 inhibitors in human plasma using LC–MS/MS. J. Pharm. Biomed. Anal. 2019b; 175: 112790–112799.
Sharif S., Bashir R., Adnan A., Mansoor S., Ahmad I., Ch AR., Tahir MS. Stability indicating, pH and pKa dependent HPLC–DAD method for the simultaneous determination of weakly ıonizable empagliflozin, dapagliflozin, and canagliflozin in pharmaceutical formulations. Chromatographia 2020; 83: 1453–1465
Sheldon RA. Fundamentals of green chemistry: Efficiency in reaction design. Chem. Soc. Rev. 2012; 41: 1437–1451.
Shen Y., Chen B., van Beek TA. Alternative solvents can make preparative liquid chromatography greener. Green Chem. 2015; 17: 4073–4081.
Snyder LR., Kirkland JJ., Dolan JW. Introduction to modern liquid chromatography; John Wiley & Sons, Inc.: Hoboken, NJ, USA: 2009; ISBN 978-0-470-50818-3.
Thakor NS., Amrutkar SV., Chaudhari PD. Simultaneous estimation of empagliflozin and metformin by high-performance thin-layer chromatography using quality-by-design approach. J. Planar Chromatogr. 2019; 32: 295–307.
Tobiszewski M., Mechlińska A., Namieśnik J. Green analytical chemistry—Theory and practice. Chem. Soc. Rev. 2010; 39: 2869–2878.
Tobiszewski M., Marć M., Gałuszka A., Namieśnik J. Green chemistry metrics with special reference to green analytical chemistry. Molecules 2015; 20: 10928–10946.
Tobiszewski M. Metrics for green analytical chemistry. Anal. Methods 2016; 8: 2993–2999.
Validation of analytical procedures: text and methodology Q2(R1)-ICH harmonized tripartite guideline. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use; 2005
Van der Aart-van AB., Wessels AMA., Heerspink HJ., Touw DJ. Simple, fast and robust LC-MS/MS method for the simultaneous quantification of canagliflozin, dapagliflozin and empagliflozin in human plasma and urine. J. Chromatogr. B 2020; 1152: 122257.
Welch CJ., Wu N., Biba M., Hartman R., Brkovic T., Gong X., Helmy R., Schafer W., Cuff J., Pirzada Z. Greening analytical chromatography. TrAC Trends Anal. Chem. 2010; 29: 667–680.
Wittich CM., Beckman TJ. Mayo clinic ınternal medicine board review, 12th ed.; Oxford University Press: Oxford, UK 2020; 168–225.

Toplam 47 adet kaynakça vardır.

Ayrıntılar

Birincil Dil	İngilizce
Konular	Enstrümantal Yöntemler
Bölüm	Araştırma Makaleleri (RESEARCH ARTICLES)
Yazarlar	İbrahim Bulduk 0000-0001-6172-7738 Erten Akbel 0000-0002-6954-3658 Serdar Güngör 0000-0003-2062-2424 Süleyman Gökce 0000-0001-9744-0245
Yayımlanma Tarihi	16 Haziran 2025
Gönderilme Tarihi	31 Ocak 2025
Kabul Tarihi	16 Mart 2025
Yayımlandığı Sayı	Yıl 2025 Cilt: 8 Sayı: 3

Kaynak Göster

APA	Bulduk, İ., Akbel, E., Güngör, S., Gökce, S. (2025). Development and Validation of A Green HPLC Method for Estimation of Empagliflozin in Pharmaceutical Products. Osmaniye Korkut Ata Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 8(3), 1333-1352. https://doi.org/10.47495/okufbed.1626492
AMA	Bulduk İ, Akbel E, Güngör S, Gökce S. Development and Validation of A Green HPLC Method for Estimation of Empagliflozin in Pharmaceutical Products. Osmaniye Korkut Ata University Journal of The Institute of Science and Techno. Haziran 2025;8(3):1333-1352. doi:10.47495/okufbed.1626492
Chicago	Bulduk, İbrahim, Erten Akbel, Serdar Güngör, ve Süleyman Gökce. “Development and Validation of A Green HPLC Method for Estimation of Empagliflozin in Pharmaceutical Products”. Osmaniye Korkut Ata Üniversitesi Fen Bilimleri Enstitüsü Dergisi 8, sy. 3 (Haziran 2025): 1333-52. https://doi.org/10.47495/okufbed.1626492.
EndNote	Bulduk İ, Akbel E, Güngör S, Gökce S (01 Haziran 2025) Development and Validation of A Green HPLC Method for Estimation of Empagliflozin in Pharmaceutical Products. Osmaniye Korkut Ata Üniversitesi Fen Bilimleri Enstitüsü Dergisi 8 3 1333–1352.
IEEE	İ. Bulduk, E. Akbel, S. Güngör, ve S. Gökce, “Development and Validation of A Green HPLC Method for Estimation of Empagliflozin in Pharmaceutical Products”, Osmaniye Korkut Ata University Journal of The Institute of Science and Techno, c. 8, sy. 3, ss. 1333–1352, 2025, doi: 10.47495/okufbed.1626492.
ISNAD	Bulduk, İbrahim vd. “Development and Validation of A Green HPLC Method for Estimation of Empagliflozin in Pharmaceutical Products”. Osmaniye Korkut Ata Üniversitesi Fen Bilimleri Enstitüsü Dergisi 8/3 (Haziran 2025), 1333-1352. https://doi.org/10.47495/okufbed.1626492.
JAMA	Bulduk İ, Akbel E, Güngör S, Gökce S. Development and Validation of A Green HPLC Method for Estimation of Empagliflozin in Pharmaceutical Products. Osmaniye Korkut Ata University Journal of The Institute of Science and Techno. 2025;8:1333–1352.
MLA	Bulduk, İbrahim vd. “Development and Validation of A Green HPLC Method for Estimation of Empagliflozin in Pharmaceutical Products”. Osmaniye Korkut Ata Üniversitesi Fen Bilimleri Enstitüsü Dergisi, c. 8, sy. 3, 2025, ss. 1333-52, doi:10.47495/okufbed.1626492.
Vancouver	Bulduk İ, Akbel E, Güngör S, Gökce S. Development and Validation of A Green HPLC Method for Estimation of Empagliflozin in Pharmaceutical Products. Osmaniye Korkut Ata University Journal of The Institute of Science and Techno. 2025;8(3):1333-52.