Abstract
Background: Type 2 diabetes mellitus is an expanding health problem. Binary antidiabetic combinations of Metformin Hydrochloride (MET) with either Saxagliptin Hydrochloride (SAX), or Dapagliflozin (DAP) are widely used. Review of the literature revealed that no single HPTLC method has been reported for the simultaneous determination of MET, SAX, and DAP allowing the determination of binary mixtures of any two of the three cited drugs in their tablets using the same experimental conditions, an important advantage for quality control. The advantages of HPTLC method relies on the simultaneous analysis of a large number of samples in a shorter analysis time, less solvent consumption, and less expenses, compared with HPLC.
Objective: The objective of the proposed method is to develop and validate a single and simple HPTLC densitometric method for the simultaneous determination of MET, SAX, and DAP.
Methods: Separation was performed using aluminum HPTLC sheets coated with silica gel 60 F254 with a mobile phase consisting of a mixture of acetonitrile: 1% w/v ammonium acetate in methanol (9: 1, v/v). Scanning was performed at 210 nm.
Results and Discussion: Linearity of the method was assessed in the concentration range of 0.25-10 μg/band for SAX and DAP and 0.25-25 μg/band for MET. The method was fully validated as per the ICH guidelines. The proposed method provided error and deviation values of less than 2% assessing good accuracy and precision.
Conclusion: The method was successfully applied to the analysis of pharmaceutical tablets of MET/SAX, MET/DAP, and SAX/DAP with high specificity.
Keywords: Dapagliflozin, ICH guidelines, HPTLC, metformin, pharmaceutical tablets, pharmaceuticals, saxagliptin.
Graphical Abstract
[1]
DeFronzo, R.A.; Ferrannini, E.; Groop, L.; Henry, R.R.; Herman, W.H.; Holst, J.J.; Hu, F.B.; Kahn, C.R.; Raz, I.; Shulman, G.I.; Simonson, D.C.; Testa, M.A.; Weiss, R. Type 2 diabetes mellitus Nat. Rev.,, 2015, 1-22. Article number: 15019
[http://dx.doi.org/10.1038/nrdp.2015.19]
[http://dx.doi.org/10.1038/nrdp.2015.19]
[2]
Stratton, I.M.; Adler, A.I.; Neil, H.A.; Matthews, D.R.; Manley, S.E.; Cull, C.A.; Hadden, D.; Turner, R.C.; Holman, R.R. Association
of glycaemia with macrovascular and microvas-cular complications
of type 2 diabetes (UKPDS 35): Prospec-tive observational
study BMJ, 2000, 12, 321(7258), 405-412.
[3]
Olokoba, A.B.; Obateru, O.A.; Olokoba, L.B. Type 2 diabetes mellitus: a review of current trends. Oman Med. J., 2012, 27(4), 269-273.
[http://dx.doi.org/10.5001/omj.2012.68] [PMID: 23071876]
[http://dx.doi.org/10.5001/omj.2012.68] [PMID: 23071876]
[4]
Li, C.J.; Liu, X.J.; Bai, L.; Yu, Q.; Zhang, Q.M.; Yu, P.; Yu, D.M. Efficacy and safety of vildagliptin, Saxagliptin or Sitagliptin as add-on therapy in Chinese patients with type 2 diabetes inadequately controlled with dual combination of traditional oral hypoglycemic agents. Diabetol. Metab. Syndr., 2014, 6, 69.
[http://dx.doi.org/10.1186/1758-5996-6-69] [PMID: 24917890]
[http://dx.doi.org/10.1186/1758-5996-6-69] [PMID: 24917890]
[5]
Qaseem, A.; Humphrey, L.L.; Sweet, D.E.; Starkey, M.; Shekelle, P. Clinical Guidelines Committee of the American College of Physicians.
Oral pharmacologic treatment of type 2 diabetes mellitus:
A clinical practice guideline from the American College of Physicians. Ann. Intern. Med., 2012, 156(3), 218-231.
[http://dx.doi.org/10.7326/0003-4819-156-3-201202070-00011] [PMID: 22312141]
[http://dx.doi.org/10.7326/0003-4819-156-3-201202070-00011] [PMID: 22312141]
[6]
Kim, Y.D.; Park, K.G.; Lee, Y.S.; Park, Y.Y.; Kim, D.K.; Nedumaran, B.; Jang, W.G.; Cho, W.J.; Ha, J.; Lee, I.K.; Lee, C.H.; Choi, H.S. Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan nuclear receptor SHP. Diabetes, 2008, 57(2), 306-314.
[http://dx.doi.org/10.2337/db07-0381] [PMID: 17909097]
[http://dx.doi.org/10.2337/db07-0381] [PMID: 17909097]
[7]
Balakumar, P.; Sundram, K.; Dhanaraj, S.A. Dapagliflozin: glucuretic action and beyond. Pharmacol. Res., 2014, 82, 34-39.
[http://dx.doi.org/10.1016/j.phrs.2014.03.008] [PMID: 24705156]
[http://dx.doi.org/10.1016/j.phrs.2014.03.008] [PMID: 24705156]
[8]
Madaan, T.; Akhtar, M.; Najmi, A.K. Sodium glucose CoTransporter 2 (SGLT2) inhibitors: Current status and future perspective. Eur. J. Pharm. Sci., 2016, 93, 244-252.
[http://dx.doi.org/10.1016/j.ejps.2016.08.025] [PMID: 27531551]
[http://dx.doi.org/10.1016/j.ejps.2016.08.025] [PMID: 27531551]
[9]
Bonadonna, R.C.; Borghi, C.; Consoli, A.; Volpe, M. Novel antidiabetic drugs and cardiovascular risk: Primum non nocere. Nutr. Metab. Cardiovasc. Dis., 2016, 26(9), 759-766.
[http://dx.doi.org/10.1016/j.numecd.2016.05.007] [PMID: 27373139]
[http://dx.doi.org/10.1016/j.numecd.2016.05.007] [PMID: 27373139]
[10]
Di Lullo, L.; Mangano, M.; Ronco, C.; Barbera, V.; De Pascalis, A.; Bellasi, A.; Russo, D.; Di Iorio, B.; Cozzolino, M. The treatment of type 2 diabetes mellitus in patients with chronic kidney disease: What to expect from new oral hypoglycemic agents. Diabetes Metab. Syndr., 2017, 11(Suppl. 1), S295-S305.
[http://dx.doi.org/10.1016/j.dsx.2017.03.005] [PMID: 28292575]
[http://dx.doi.org/10.1016/j.dsx.2017.03.005] [PMID: 28292575]
[11]
Goldenberg, R.M.; Verma, S.; Perkins, B.A.; Gilbert, J.D.; Zinman, B. Can the combination of incretin agents and sodium glucose cotransporter 2 (SGLT2) inhibitors reconcile the yin and yang of glucagon? Can. J. Diabetes, 2017, 41(1), 6-9.
[http://dx.doi.org/10.1016/j.jcjd.2016.08.001] [PMID: 27838228]
[http://dx.doi.org/10.1016/j.jcjd.2016.08.001] [PMID: 27838228]
[12]
Vakkalagadda, B.; Vetter, M.L.; Rana, J.; Smith, C.H.; Huang, J.; Karkas, J.; Boulton, D.W.; LaCreta, F. Bioequivalence of saxagliptin/dapagliflozin fixed-dose combination tablets compared with coadministration of the individual tablets to healthy subjects. Pharmacol. Res. Perspect., 2016, 3(6)e00201
[http://dx.doi.org/10.1002/prp2.201] [PMID: 27022473]
[http://dx.doi.org/10.1002/prp2.201] [PMID: 27022473]
[13]
Jani, B.R.; Shah, K.V.; Kapupara, P.P. Development and validation of UV spectroscopic method for simultaneous estimation of dapagliflozin and metformin hydrochloride in synthetic mixture. Int. J. Res. Dev. Pharm. Life Sci., 2015, 4(3), 1569-1576.
[14]
Raveendra, B.G.; Kumar, R.A.; Shaheen, S.D.; Greeshma, A.; Satyanarayana, M.; Manikanta, R.S.H.T.; Syam, C.P.B. A novel stability-indicating method for the simultaneous estimation of saxagliptin and dapagliflozin in rat serum by using UV spectroscopy. Pharm. Anal. Acta, 2018, 9, 579.
[15]
Parmar, S.H.; Luhar, S.V.; Narkhede, S.B. Development and validation of UV-spectroscopic first derivative and high performance thin layer chromatography analytical methods for simultaneous estimation of dapagliflozin propanediol monohydrate and saxagliptin hydrochloride in synthetic mixture. Ejbps, 2018, 5(5), 668-684.
[16]
Merey, H.A.; Ramadan, N.K.; Diab, S.S.; Moustafa, A.A. Chromatographic methods for the simultaneous determination of binary mixture of saxagliptin HCl and metformin HCl. Bull. Fac. Pharm. Cairo Univ., 2017, 55, 311-317.
[http://dx.doi.org/10.1016/j.bfopcu.2017.04.002]
[http://dx.doi.org/10.1016/j.bfopcu.2017.04.002]
[17]
Prasad, P.B.N.; Satyanaryana, K.; Krishnamohan, G. Development and validation of a method for simultaneous determination of metformin and saxagliptin in a formulation by RP-HPLC. Am. J. Anal. Chem., 2015, 6, 841-850.
[http://dx.doi.org/10.4236/ajac.2015.611080]
[http://dx.doi.org/10.4236/ajac.2015.611080]
[18]
Patel, K.J.; Chaudhary, A.B.; Bhadani, S.M.; Raval, R.J. Stability indicating RP-HPLC method development and validation for estimation of dapagliflozin and metformin HCl. WJPPS, 2017, 6(9), 796-809.
[http://dx.doi.org/10.20959/wjpps20179-9638]
[http://dx.doi.org/10.20959/wjpps20179-9638]
[19]
Patel, P.D.; Pandya, S.S.; Validated, R.P. HPLC method for simultaneous estimation of dapagliflozin and saxagliptin hydrochloride in tablet dosage form. IJPRS, 2018, 7(1), 9-15.
[http://dx.doi.org/10.31638/IJPRS.V7.I1.00006]
[http://dx.doi.org/10.31638/IJPRS.V7.I1.00006]
[20]
Deepan, T.; Dhanaraju, M.D. Stability indicating HPLC method for the simultaneous determination of dapagliflozin and saxagliptin in bulk and tablet dosage form. Curr. Issues Pharm. Med. Sci., 2018, 31(1), 39-43.
[http://dx.doi.org/10.1515/cipms-2018-0009]
[http://dx.doi.org/10.1515/cipms-2018-0009]
[21]
Walode, S.G.; Kasture, A.V. Quantitative planner chromatographic method development for sitagliptin phosphate monohydrate and metformin hydrochloride in presence of their degradation product. Asian J. Res. Chem, 2015, 8(7), 472-480.
[http://dx.doi.org/10.5958/0974-4150.2015.00076.0]
[http://dx.doi.org/10.5958/0974-4150.2015.00076.0]
[22]
Srivani, J.; Umamahesh, B.; Veeresham, C. Development and validation of stability indicating HPTLC method for simultaneous determination of linagliptin and metformin. Int. J. Pharm. Pharm. Sci., 2016, 8(1), 112-115.
[23]
Havel, S.S.; Dhaneshwar, S.R. Application of high performance thin layer chromatography-densitometry for the simultaneous determination of metformin hydrochloride and glipizide in bulk drug and tablet formulation. Pharm. Sin., 2011, 2(1), 40-48.
[24]
El-Kimary, E.I.; Hamdy, D.A.; Mourad, S.S.; Barary, M.A. HPTLC determination of three gliptins in binary mixtures with metformin. J. Chromatogr. Sci., 2016, 54(1), 79-87.
[PMID: 26223462]
[PMID: 26223462]
[25]
Dhaneshwar, S.R.; Salunkhe, J.V.; Bhusari, V.K. Validated HPTLC method for simultaneous estimation of met-formin hydrochloride, atorvastatin and glimepiride in bulk drug and formulation. J. Anal. Bioanal. Tech, 2010, 1, 109, 5.
[26]
Alagawadi, K.R.; Kumar, A.M. HPTLC method for the simultaneous estimation of atorvastatin, glimipride and metformin in combined dosage form. JPBMS, 2010, 07(07), 4.
[27]
Modi, D.K.; Patel, B.H. Simultaneous determination of metformin hydrochloride and glipizide in tablet formulation by HPTLC. J. Liq. Chromatogr. Relat. Technol., 2012, 35, 28-39.
[http://dx.doi.org/10.1080/10826076.2011.593227]
[http://dx.doi.org/10.1080/10826076.2011.593227]
[28]
Sharma, K.; Parle, A. Development and validation of HPTLC method for simultaneous estimation of metformin hydrochloride and alogliptin benzoate in bulk drugs and combined dosage forms. Der Pharmacia Lettre, 2015, 7(7), 321-328.
[29]
Srividya, S.; Swetha, E.; Veeresham, C. Development and validation of a high performance thin layer chromatographic method for quantitative analysis of saxagliptin. Am. J. Anal. Chem., 2015, 6, 797-806.
[http://dx.doi.org/10.4236/ajac.2015.610076]
[http://dx.doi.org/10.4236/ajac.2015.610076]
[30]
Electronic Medicines Compendium (Emc) https://www.medicines. org.uk/emc/product/2312/smpc (Accessed Oct. 2018)
[31]
ICH 23. ICH, Validation of analytical procedures: Text and methodology
Q2 (R1)., In International Conference on Har-monisation,
Geneva,. 2005.http://www.ich.org/fileadmin/Public_Web_Site/ ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf (Accessed Oct. 2018)
[32]
Miller, J.N.; Miller, J.C. Statistics and chemometrics for analytical chemistry, 4th ed; Prentice Hall: Harlow, England, 2000.
[33]
Material, S. Supplementary Material (ESI) for Green Chemistry,
The Roy-al Society of Chemistry 2010, GSK Solvent Selection
Guide. 2009.http://www.rsc.org/suppdata/gc/c0/c0gc00918k/c0gc 00918k.pdf (Accessed Oct. 2018)
[34]
Prat, D.; Haylerb, J.; Wellsc, A. A survey of solvent selection guides. Green Chem., 2014, 16, 4546.
[http://dx.doi.org/10.1039/C4GC01149J]
[http://dx.doi.org/10.1039/C4GC01149J]
[35]
Hazardous substance fact sheet, New Jersey department of health https://nj.gov/health/eoh/rtkweb/documents/fs/0084.pdf (Accessed Oct. 2018)
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