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Farklı Matrislerde Pioglitazon ve Metforminin Yüksek Performanslı Sıvı Kromatografi Yöntemleri ile Nicel Analizine Yönelik Güncel Yaklaşımlar

Yıl 2025, Cilt: 2 Sayı: 4, 1 - 30, 25.12.2025

Öz

Diyabet, sıklıkla karşılaşılan ve yüksek ölüm oranına sahip bir hastalıktır. Pankreasın beta hücrelerinin tahrip olması sonucu pankreastan insülin salgılanamaması veya insüline karşı direnç gelişmesiyle insülin görevini yapamaz hale gelir ve sonuç olarak hastalık yüksek glikoz seviyesi ile karekterize olur. Vakaların büyük çoğunluğunu insüline bağımlı olmayan (tip 2) diyabet oluşturur. Diyabet çoğu zaman asemptomatik olsa da klinik belirtileri, poliüri, polidipsi, polifaji ve açıklanamayan kilo kaybı şeklinde sıralanabilir. Komplikasyonları arasında, ülserler, ampütasyonlar, retinopati, böbrek yetmezliği ve kalp hastalıkları sıralanabilir.
Diyabet hastalığının tedavisinde hedef glikoz seviyesini azaltmak veya korumaktır. Bu amaçla hastaya ilk olarak, egzersiz ve diyet değişikliği ile yaşam tarzı değişiklikleri önerilir. Glikoz düzeyi, bu tavsiyeler ile düzenlenmiyorsa hastaya oral antidiyabetik ajan kullanması önerilir.
Bu çalışmada, diyabet tedavisinde kullanılan oral antidiyabetik ajanlardan metformin ve pioglitazonun, analitik kimyada sıklıkla kullanılan bir kromatografik yöntem olan HPLC ile yapılan miktar analizlerine yer verilmiştir.

Kaynakça

  • Amini, H., Ahmadiani, A., & Gazerani, P. (2005). Determination of metformin in human plasma by high-performance liquid chromatography. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 824(1–2), 319–322. https://doi.org/10.1016/j.jchromb.2005.07.009 28
  • Antar, S. A., Ashour, N. A., Sharaky, M., Khattab, M., Ashour, N. A., Zaid, R. T., … & Al- Karmalawy, A. A. (2023). Diabetes mellitus: Classification, mediators, and complications; A gate to identify potential targets for the development of new effective treatments. Biomedicine & Pharmacotherapy, 168, 115734. https://doi.org/10.1016/J.BIOPHA.2023.115734
  • Aydin, İ., ve Narı̇n, İ. (2017). Deksketoprofen trometamol ve diklofenak sodyumun farmasötik örneklerde DAD dedektörlü HPLC ile eşzamanlı tayini. Sağlık Bilimleri Dergisi, 26(1), 47–51.
  • Bruns, D. E., Ashwood, E. R., & Carl, A. B. (2007). Fundamentals of Molecular Diagnostics.Elsevier Health Sciences.
  • Cheng, C. L., & Chou, C. H. (2001). Determination of metformin in human plasma by high- performance liquid chromatography with spectrophotometric detection. Journal of Chromatography B: Biomedical Sciences and Applications, 762(1), 51–58. https://doi.org/10.1016/S0378-4347(01)00342-5
  • da Trindade, M. T., Kogawa, A. C., & Salgado, H. R. N. (2018). Metformin: A Review of Characteristics, Properties, Analytical Methods and Impact in the Green Chemistry. Critical Reviews in Analytical Chemistry, 48(1), 66–72. https://doi.org/10.1080/10408347.2017.1374165
  • Dahlén, A. D., Dashi, G., Maslov, I., Attwood, M. M., Jonsson, J., Trukhan, V., & Schiöth, H. B. (2022). Trends in Antidiabetic Drug Discovery: FDA Approved Drugs, New Drugs in Clinical Trials and Global Sales. Frontiers in Pharmacology, 12, 807548. https://doi.org/10.3389/FPHAR.2021.807548/FULL
  • Eckland, D. A., & Danhof, M. (2000). Clinical pharmacokinetics of pioglitazone. Experimental and Clinical Endocrinology and Diabetes, 108(2), 234–242. https://doi.org/10.1055/s- 2000-8525
  • Fung, E. (2008). Protein Arrays: Methods and Protocols. Springer Science & Business Media.
  • Gault, V. A., & McClenaghan, N. H. (2013). Understanding Bioanalytical Chemistry: Principles and Applications - Victor A. Gault, Neville H. McClenaghan - Google Kitaplar. John Wiley & Sons.
  • Gillies, P. S., & Dunn, C. J. (2000). Pioglitazone. Drugs, 60(2), 333–343. https://doi.org/10.2165/00003495-200060020-00009/METRICS
  • Görög, S. (2008). Drug safety, drug quality, drug analysis. Journal of Pharmaceutical and Biomedical Analysis, 48(2), 247–253. https://doi.org/10.1016/J.JPBA.2007.10.038
  • Graham, G. G., Punt, J., Arora, M., Day, R. O., Doogue, M. P., Duong, J. K., … & Williams, K. M. (2011, September). Clinical pharmacokinetics of metformin. Clinical Pharmacokinetics, Vol. 50, pp. 81–98. Springer. https://doi.org/10.2165/11534750- 000000000-00000
  • Hubert, P., Nguyen-Huu, J. J., Boulanger, B., Chapuzet, E., Chiap, P., Cohen, N., … & Rozet, E. (2007). Harmonization of strategies for the validation of quantitative analytical procedures. A SFSTP proposal - Part II. Journal of Pharmaceutical and Biomedical 29 Analysis, 45(1), 70–81. https://doi.org/10.1016/j.jpba.2007.06.013
  • International Council for Harmonisation. (2005). Validation of analytical procedures: Text and methodology Q2(R1). https://www.ich.org/page/quality-guidelines
  • Islambulchilar, Z., Valizadeh, H., & Zakeri-Milani, P. (2010). Rapid HPLC Determination of Pioglitazone in Human Plasma by Protein Precipitation and Its Application to Pharmacokinetic Studies. Journal of AOAC INTERNATIONAL, 93(3), 876–881. https://doi.org/10.1093/jaoac/93.3.876
  • Jain, D., Jain, S., Jain, D., & Amin, M. (2008). Simultaneous estimation of metformin hydrochloride, pioglitazone hydrochloride, and glimepiride by RP-HPLC in tablet formulation. Journal of Chromatographic Science, 46(6), 501–504. https://doi.org/10.1093/chromsci/46.6.501
  • Krieter, P. A., Colletti, A. E., Doss, G. A., & Miller, R. R. (1994). Disposition and metabolism of the hypoglycemic agent pioglitazone in rats. Drug Metabolism and Disposition, 22(4), 625-630.
  • Lakshmi, K. S., Rajesh, T., & Sharma, S. (2009). Simultaneous determination of metformin and pioglitazone by reversed phase HPLC in pharmaceutical dosage forms. International Journal of Pharmacy and Pharmaceutical Sciences, 1(2), 162–166.
  • Musi, N., Hirshman, M. F., Nygren, J., Svanfeldt, M., Bavenholm, P., Rooyackers, O., … & Goodyear, L. J. (2002). Metformin increases AMP-activated protein-kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes, 51(7), 2074–2081. https://doi.org/10.2337/diabetes.51.7.2074
  • Nalbalwar, N. N. (2015). HPLC method development and validation-A general Concept. International Journal of Chemical and Pharmaceutical Sciences, 6(1), 8-14.
  • Pandit, V., Pai, R. S., Singh, G., Devi, K., Narayana, S., & Suresh, S. (2012). Development and validation of the liquid chromatographic method for simultaneous estimation of metformin, pioglitazone, and glimepiride in pharmaceutical dosage forms. Pharmaceutical Methods, 3(1), 9–13. https://doi.org/10.4103/2229-4708.97707
  • Panigrahy, U. P., & Reddy, A. S. K. (2015). A novel validated RP-HPLC-DAD method for the simultaneous estimation of Metformin Hydrochloride and Canagliflozin in bulk and pharmaceutical tablet dosage form with forced degradation studies. Orient J Chem, 31(3), 1489–1507.
  • Pernicova, I., & Korbonits, M. (2014). Metformin-mode of action and clinical implications for diabetes and cancer. Nature Revıews | Endocrınology, 10, 143–156. https://doi.org/10.1038/nrendo.2013.256
  • Phung, O. J., Sood, N. A., Sill, B. E., & Coleman, C. I. (2011). Oral anti-diabetic drugs for the prevention of Type 2 diabetes. Diabetic Medicine, 28(8), 948–964. https://doi.org/10.1111/j.1464-5491.2011.03303.x
  • Rena, G., Pearson, E. R., & Sakamoto, K. (2013). Molecular mechanism of action of metformin: old or new insights? Diabetologia, 56(9), 1898–1906. https://doi.org/10.1007/s00125- 013-2991-0
  • Saber, A. L. (2008). Determination of pioglitazone hydrochloride in tablets by High- 30 Performance Liquid Chromatography. Pakistan Journal of Analytical & Environmental Chemistry, 9(2), 118–121.
  • Sepici Dinçel, A., ve Eser, B. (2018). Kromatografiye giriş, yüksek performanslı sıvı kromatografi kullanımında basit ipuçları. Sağlık Hizmetleri ve Eğitimi Dergisi, 2(2), 51– 57. https://doi.org/10.26567/JOHSE.2018250150
  • Skoog, D. A., Holler, F. J., & Crouch, S. R. (2019). Principles of instrumental analysis (6thed.). Boston, MA: Cengage Learning.
  • Snyder, L. R., Joseph, J. K., & Glajch, J. L. (2012). Practical HPLC Method Development. John Wiley & Sons.
  • Sripalakit, P., Neamhom, P., & Saraphanchotiwitthaya, A. (2006). High-performance liquid chromatographic method for the determination of pioglitazone in human plasma using ultraviolet detection and its application to a pharmacokinetic study. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 843(2), 164–169. https://doi.org/10.1016/j.jchromb.2006.05.032
  • Swartz, M. E., & Krull, I. S. (2012). Handbook of analytical validation. CRC Press.
  • Sweetman, S. (2010). Martindale: The Complete Drug Reference Online via Medicines Complete. Pharmaceutical Press.
  • Tache, F., David, V., Farca, A., & Medvedovici, A. (2001). HPLC-DAD determination of Metformin in human plasma using derivatization with p-nitrobenzoyl chloride in a biphasic system. Microchemical Journal, 68(1), 13–19. https://doi.org/10.1016/S0026- 265X(00)00170-3
  • British Pharmacopoeia Commission. (1864). The British Pharmacopoeia. London: Spottiswoode & Co.
  • Tomic, D., Shaw, J. E., & Magliano, D. J. (2022). The burden and risks of emerging complications of diabetes mellitus. Nature Reviews Endocrinology 2022 18:9, 18(9), 525–539. https://doi.org/10.1038/s41574-022-00690-7
  • Turner, R. (1998). Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet, 352(9131), 854–865. https://doi.org/10.1016/S0140-6736(98)07037-8
  • US Food and Drug Administration (US FDA). (2018). Bioanalytical Method Validation Guidance for Industry. Retrieved from https://www.fda.gov/regulatory- information/search-fda-guidance-documents/bioanalytical-method-validation- guidance-industry
  • Zhang, M., Moore, G. A., Lever, M., Gardiner, S. J., Kirkpatrick, C. M. J., & Begg, E. J. (2002). Rapid and simple high-performance liquid chromatographic assay for the determination of metformin in human plasma and breast milk. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 766(1), 175–179. https://doi.org/10.1016/S0378-4347(01)00430-3

Current Approaches to Quantitative Analysis of Pioglitazone and Metformin in Different Matrices by High-Performance Liquid Chromatography Methods

Yıl 2025, Cilt: 2 Sayı: 4, 1 - 30, 25.12.2025

Öz

Diabetes is a common disease with a high mortality rate. Damage to the pancreatic beta cells results in the pancreas failing to secrete insulin or developing insulin resistance, rendering insulin unable to function effectively. Consequently, the disease is characterized by high glucose levels. Non-insulin-dependent (type 2) diabetes accounts for most cases. While diabetes is often asymptomatic, clinical symptoms include polyuria, polydipsia, polyphagia, and unexplained weight loss. Complications include ulcers, amputations, retinopathy, renal failure, and heart disease.
The goal of treating diabetes is to reduce or maintain glucose levels. To this end, patients are initially advised to make lifestyle changes, including exercise and dietary changes. If glucose levels are not controlled with these recommendations, oral antidiabetic agents are recommended.
This study includes quantitative analyses of metformin and pioglitazone, oral antidiabetic agents used in the treatment of diabetes, using HPLC, a chromatographic method frequently used in analytical chemistry.

Kaynakça

  • Amini, H., Ahmadiani, A., & Gazerani, P. (2005). Determination of metformin in human plasma by high-performance liquid chromatography. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 824(1–2), 319–322. https://doi.org/10.1016/j.jchromb.2005.07.009 28
  • Antar, S. A., Ashour, N. A., Sharaky, M., Khattab, M., Ashour, N. A., Zaid, R. T., … & Al- Karmalawy, A. A. (2023). Diabetes mellitus: Classification, mediators, and complications; A gate to identify potential targets for the development of new effective treatments. Biomedicine & Pharmacotherapy, 168, 115734. https://doi.org/10.1016/J.BIOPHA.2023.115734
  • Aydin, İ., ve Narı̇n, İ. (2017). Deksketoprofen trometamol ve diklofenak sodyumun farmasötik örneklerde DAD dedektörlü HPLC ile eşzamanlı tayini. Sağlık Bilimleri Dergisi, 26(1), 47–51.
  • Bruns, D. E., Ashwood, E. R., & Carl, A. B. (2007). Fundamentals of Molecular Diagnostics.Elsevier Health Sciences.
  • Cheng, C. L., & Chou, C. H. (2001). Determination of metformin in human plasma by high- performance liquid chromatography with spectrophotometric detection. Journal of Chromatography B: Biomedical Sciences and Applications, 762(1), 51–58. https://doi.org/10.1016/S0378-4347(01)00342-5
  • da Trindade, M. T., Kogawa, A. C., & Salgado, H. R. N. (2018). Metformin: A Review of Characteristics, Properties, Analytical Methods and Impact in the Green Chemistry. Critical Reviews in Analytical Chemistry, 48(1), 66–72. https://doi.org/10.1080/10408347.2017.1374165
  • Dahlén, A. D., Dashi, G., Maslov, I., Attwood, M. M., Jonsson, J., Trukhan, V., & Schiöth, H. B. (2022). Trends in Antidiabetic Drug Discovery: FDA Approved Drugs, New Drugs in Clinical Trials and Global Sales. Frontiers in Pharmacology, 12, 807548. https://doi.org/10.3389/FPHAR.2021.807548/FULL
  • Eckland, D. A., & Danhof, M. (2000). Clinical pharmacokinetics of pioglitazone. Experimental and Clinical Endocrinology and Diabetes, 108(2), 234–242. https://doi.org/10.1055/s- 2000-8525
  • Fung, E. (2008). Protein Arrays: Methods and Protocols. Springer Science & Business Media.
  • Gault, V. A., & McClenaghan, N. H. (2013). Understanding Bioanalytical Chemistry: Principles and Applications - Victor A. Gault, Neville H. McClenaghan - Google Kitaplar. John Wiley & Sons.
  • Gillies, P. S., & Dunn, C. J. (2000). Pioglitazone. Drugs, 60(2), 333–343. https://doi.org/10.2165/00003495-200060020-00009/METRICS
  • Görög, S. (2008). Drug safety, drug quality, drug analysis. Journal of Pharmaceutical and Biomedical Analysis, 48(2), 247–253. https://doi.org/10.1016/J.JPBA.2007.10.038
  • Graham, G. G., Punt, J., Arora, M., Day, R. O., Doogue, M. P., Duong, J. K., … & Williams, K. M. (2011, September). Clinical pharmacokinetics of metformin. Clinical Pharmacokinetics, Vol. 50, pp. 81–98. Springer. https://doi.org/10.2165/11534750- 000000000-00000
  • Hubert, P., Nguyen-Huu, J. J., Boulanger, B., Chapuzet, E., Chiap, P., Cohen, N., … & Rozet, E. (2007). Harmonization of strategies for the validation of quantitative analytical procedures. A SFSTP proposal - Part II. Journal of Pharmaceutical and Biomedical 29 Analysis, 45(1), 70–81. https://doi.org/10.1016/j.jpba.2007.06.013
  • International Council for Harmonisation. (2005). Validation of analytical procedures: Text and methodology Q2(R1). https://www.ich.org/page/quality-guidelines
  • Islambulchilar, Z., Valizadeh, H., & Zakeri-Milani, P. (2010). Rapid HPLC Determination of Pioglitazone in Human Plasma by Protein Precipitation and Its Application to Pharmacokinetic Studies. Journal of AOAC INTERNATIONAL, 93(3), 876–881. https://doi.org/10.1093/jaoac/93.3.876
  • Jain, D., Jain, S., Jain, D., & Amin, M. (2008). Simultaneous estimation of metformin hydrochloride, pioglitazone hydrochloride, and glimepiride by RP-HPLC in tablet formulation. Journal of Chromatographic Science, 46(6), 501–504. https://doi.org/10.1093/chromsci/46.6.501
  • Krieter, P. A., Colletti, A. E., Doss, G. A., & Miller, R. R. (1994). Disposition and metabolism of the hypoglycemic agent pioglitazone in rats. Drug Metabolism and Disposition, 22(4), 625-630.
  • Lakshmi, K. S., Rajesh, T., & Sharma, S. (2009). Simultaneous determination of metformin and pioglitazone by reversed phase HPLC in pharmaceutical dosage forms. International Journal of Pharmacy and Pharmaceutical Sciences, 1(2), 162–166.
  • Musi, N., Hirshman, M. F., Nygren, J., Svanfeldt, M., Bavenholm, P., Rooyackers, O., … & Goodyear, L. J. (2002). Metformin increases AMP-activated protein-kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes, 51(7), 2074–2081. https://doi.org/10.2337/diabetes.51.7.2074
  • Nalbalwar, N. N. (2015). HPLC method development and validation-A general Concept. International Journal of Chemical and Pharmaceutical Sciences, 6(1), 8-14.
  • Pandit, V., Pai, R. S., Singh, G., Devi, K., Narayana, S., & Suresh, S. (2012). Development and validation of the liquid chromatographic method for simultaneous estimation of metformin, pioglitazone, and glimepiride in pharmaceutical dosage forms. Pharmaceutical Methods, 3(1), 9–13. https://doi.org/10.4103/2229-4708.97707
  • Panigrahy, U. P., & Reddy, A. S. K. (2015). A novel validated RP-HPLC-DAD method for the simultaneous estimation of Metformin Hydrochloride and Canagliflozin in bulk and pharmaceutical tablet dosage form with forced degradation studies. Orient J Chem, 31(3), 1489–1507.
  • Pernicova, I., & Korbonits, M. (2014). Metformin-mode of action and clinical implications for diabetes and cancer. Nature Revıews | Endocrınology, 10, 143–156. https://doi.org/10.1038/nrendo.2013.256
  • Phung, O. J., Sood, N. A., Sill, B. E., & Coleman, C. I. (2011). Oral anti-diabetic drugs for the prevention of Type 2 diabetes. Diabetic Medicine, 28(8), 948–964. https://doi.org/10.1111/j.1464-5491.2011.03303.x
  • Rena, G., Pearson, E. R., & Sakamoto, K. (2013). Molecular mechanism of action of metformin: old or new insights? Diabetologia, 56(9), 1898–1906. https://doi.org/10.1007/s00125- 013-2991-0
  • Saber, A. L. (2008). Determination of pioglitazone hydrochloride in tablets by High- 30 Performance Liquid Chromatography. Pakistan Journal of Analytical & Environmental Chemistry, 9(2), 118–121.
  • Sepici Dinçel, A., ve Eser, B. (2018). Kromatografiye giriş, yüksek performanslı sıvı kromatografi kullanımında basit ipuçları. Sağlık Hizmetleri ve Eğitimi Dergisi, 2(2), 51– 57. https://doi.org/10.26567/JOHSE.2018250150
  • Skoog, D. A., Holler, F. J., & Crouch, S. R. (2019). Principles of instrumental analysis (6thed.). Boston, MA: Cengage Learning.
  • Snyder, L. R., Joseph, J. K., & Glajch, J. L. (2012). Practical HPLC Method Development. John Wiley & Sons.
  • Sripalakit, P., Neamhom, P., & Saraphanchotiwitthaya, A. (2006). High-performance liquid chromatographic method for the determination of pioglitazone in human plasma using ultraviolet detection and its application to a pharmacokinetic study. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 843(2), 164–169. https://doi.org/10.1016/j.jchromb.2006.05.032
  • Swartz, M. E., & Krull, I. S. (2012). Handbook of analytical validation. CRC Press.
  • Sweetman, S. (2010). Martindale: The Complete Drug Reference Online via Medicines Complete. Pharmaceutical Press.
  • Tache, F., David, V., Farca, A., & Medvedovici, A. (2001). HPLC-DAD determination of Metformin in human plasma using derivatization with p-nitrobenzoyl chloride in a biphasic system. Microchemical Journal, 68(1), 13–19. https://doi.org/10.1016/S0026- 265X(00)00170-3
  • British Pharmacopoeia Commission. (1864). The British Pharmacopoeia. London: Spottiswoode & Co.
  • Tomic, D., Shaw, J. E., & Magliano, D. J. (2022). The burden and risks of emerging complications of diabetes mellitus. Nature Reviews Endocrinology 2022 18:9, 18(9), 525–539. https://doi.org/10.1038/s41574-022-00690-7
  • Turner, R. (1998). Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet, 352(9131), 854–865. https://doi.org/10.1016/S0140-6736(98)07037-8
  • US Food and Drug Administration (US FDA). (2018). Bioanalytical Method Validation Guidance for Industry. Retrieved from https://www.fda.gov/regulatory- information/search-fda-guidance-documents/bioanalytical-method-validation- guidance-industry
  • Zhang, M., Moore, G. A., Lever, M., Gardiner, S. J., Kirkpatrick, C. M. J., & Begg, E. J. (2002). Rapid and simple high-performance liquid chromatographic assay for the determination of metformin in human plasma and breast milk. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 766(1), 175–179. https://doi.org/10.1016/S0378-4347(01)00430-3
Toplam 39 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Eczacılıkta Analitik Kimya
Bölüm Derleme
Yazarlar

Muhammed Mirza Yıldız 0009-0008-5028-3447

Tuğrul Çağrı Akman 0000-0002-5439-950X

Gönderilme Tarihi 31 Ekim 2025
Kabul Tarihi 19 Kasım 2025
Yayımlanma Tarihi 25 Aralık 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 2 Sayı: 4

Kaynak Göster

APA Yıldız, M. M., & Akman, T. Ç. (2025). Farklı Matrislerde Pioglitazon ve Metforminin Yüksek Performanslı Sıvı Kromatografi Yöntemleri ile Nicel Analizine Yönelik Güncel Yaklaşımlar. Erzincan Binali Yıldırım Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, 2(4), 1-30.