VALIDATED STABILITY INDICATING HPLC APPROACH FOR QUANTIFYING TRICHOLINE CITRATE AND CYPROHEPTADINE SIMULTANEOUSLY IN SYRUP FORMS
Keywords:Tricholine citrate, Cyproheptadine, Syrup form, HPLC, Stability indicating
Objective: This investigation demonstrates a stability-indicating and reliable “high-performance liquid chromatography” method to simultaneously quantify tricholine citrate (TEC) and cyproheptadine (CRH) in the syrup form and bulk form.
Methods: Successful separation was accomplished using C18 “Agilent column (250 mm × 4.6 mm, 5 μm)” with isocratic type of elution using mobile phase containing 0.1 M NaH2PO4 buffer and acetonitrile at 55% volume and 45% volume ratio, respectively with 1.0 ml/min flow rate. The wavelength sensor was attuned at 263 nm to quantify TEC and CRH.
Results: TEC and CRH peaks were eluted with fine resolution at retention times 1.837 min and 2.936 min, respectively. In the 137.5-412.5 μg/ml and 1-3 μg/ml concentration ranges for TEC and CRH, the calibration graphs were linear, with regression coefficients of 0.9999 and 0.9998, respectively. The suggested "high-performance liquid chromatography" approach has been shown as sensitive, precise, robust, accurate, specific and stability indicating through the resolution of TEC and CRH from its degradation-based compounds.
Conclusion: The established high-performance liquid chromatography technique was effectively extended to the evaluation of TEC and CRH in the combined syrup form and the test results appeared satisfactory.
Columbo M, Rohr AS. Asthma in the elderly: the effect of choline supplementation. Allergy Asthma Clin Immunol 2016;12:15.
Mehedint MG, Zeisel SH. Choline's role in maintaining liver function: new evidence for epigenetic mechanisms. Curr Opin Clin Nutr Metab Care 2013;16:339-45.
Tricholine citrate, Pubchem. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Tricholine-citrate [Last accessed on 20 Dec 2020]
Feng YM, Feng CW, Chen SY, Hsieh HY, Chen YH, Hsu CD. Cyproheptadine, an antihistaminic drug, inhibits the proliferation of hepatocellular carcinoma cells by blocking cell cycle progression through the activation of P38 MAP kinase. BMC Cancer 2015;15:134.
Kapur S, Zipursky RB, Jones C, Wilson AA, DaSilva JD, Houle S. Cyproheptadine: a potent in vivo serotonin antagonist. Am J Psychiatry 1997;154:884.
Harrison ME, Norris ML, Robinson A, Spettigue W, Morrissey M, Isserlin L. Use of cyproheptadine to stimulate appetite and body weight gain: a systematic review. Appetite 2019;137:62-72.
Ascierto PA, Marincola FM. Combination therapy: the next opportunity and challenge of medicine. J Transl Med 2011;9:115.
Ioannis Z. Improving cancer combination therapy by timing drug administration. Sci Transl Med 2020;12:eabb5671.
Fares J, Kanojia D, Rashidi A, Ulasov I, Lesniak MS. Landscape of combination therapy trials in breast cancer brain metastasis. Int J Cancer 2020;147:1939-52.
Tsioufis K, Kreutz R, Sykara G, van Vugt J, Hassan T. Impact of single-pill combination therapy on adherence, blood pressure control, and clinical outcomes: a rapid evidence assessment of recent literature. J Hypertens 2020;38:1016-28.
Cyprosal, Indiamart.com. Available from: https://www.indiamart.com/proddetail/cyproheptadine-with-tricholine-citrate-syrup-15212352255.html [Last accessed on 20 Dec 2020]
Cyprohar, Indiamart.com. Available from: https://www.indiamart.com/proddetail/cyprohar-16212742633.html [Last accessed on 20 Dec 2020]
Cyprolac T, Indiamart.com. Available from: https://www.indiamart.com/proddetail/cyproheptadine-hcl-and-tricholine-citrate-syrup-21597816088.html [Last accessed on 20 Dec 2020]
Cypro T, Indiamart.com. Available from: https://www.indiamart.com/proddetail/cyproheptadine-hydrochloride-tricholine-citrate-syrup-20411821091.html [Last accessed on 20 Dec 2020]
Clopex TC, Indiamart.com. Available from: https://www.indiamart.com/proddetail/cyproheptadine-hcl-and-tricholine-citrate-syrup-8837917048.html [Last accessed on 20 Dec 2020]
Mayuresh K, Shaheen NS, Lalit JP. Safety and efficacy of a combination of cyproheptadine and tricholine citrate: phase IV study. Ann Int Med Den Res 2018;4:1-5.
International conference on the harmonization. ICH Stability testing of new drug substances and products Q1A (R2); 2003.
International conference on the harmonization. ICH harmonized tripartite guideline. Validation of analytical procedures: Text and methodology Q2(R1); 2005.
Belal F, El-Din MKS, Tolba MM, Elmansi H. Micelle-enhanced spectrofluorimetric method for determination of cyproheptadine hydrochloride in tablets: application to in vitro drug release and content uniformity test. J Fluoresc 2014;24:85–91.
Wagh YB, Bhushan BA, Saudagar RB. Development and validation of UV spectrophotometric method for estimation of cyproheptadine hydrochloride in bulk and tablet formulation by co-solvency approach. World J Pharma Res 2016;5:1924-30.
Sayanna VT, Reddy ChVR. Determination of cyproheptadine hydrochloride in pure and pharmaceutical forms: a spectrophotometric study. Orient J Chem 2015;31:1779-86.
Maham M, Kiarostami V, Waqif Husain S, Abroomand Azar P, Tehrani MS, Khoeini SM, et al. Extraction and determination of cyproheptadine in human urine by DLLME-HPLC method. Iran J Pharm Res 2013;12:311-8.
Sadhana JR, Mansi AS. New bioanalytical HPLC method for the determination of cyproheptadine hydrochloride in human plasma and its application to rat pharmacokinetic study. Indian J Pharm Educ Res 2019;53(Suppl 2):S338-46.
Mina M, Mahnaz Q, Seyed SH, Azade S. Preconcentration and determination of cyproheptadine by using liquid phase microextraction and solvent bar in biological fluids in trace level. Biosci Biotechnol Res Asia 2015;12:521-9.
El-Din MKS, Belal F, Tolba MM, Elmansi H. Stability indicating HPLC method coupled with fluorescence detection for the determination of cyproheptadine hydrochloride in its tablets. Studies on degradation kinetics. Anal Chem Lett 2018;8:565-77.
Feas X, Ye L, Hosseini SV, Fente CA, Cepeda A. Development and validation of LC-MS/MS method for the determination of cyproheptadine in several pharmaceutical syrup formulations. J Pharm Biomed Anal 2009;50:1044-9.
Ravichandran V, Shalini S, Sundaram KM, Rajak H. Validation of analytical methods-strategies and importance. Int J Pharm Pharm Sci 2010;2:18-22.
Rode DM, Rao NN. A review on development and validation of stability indicating HPLC methods for analysis of acidic drugs. Int J Curr Pharm Res 2019;11:22-33.
Rajasingam R, Sagineedu SR, Tan YH, Nalaiya J, Pichika MR. Stress degradation studies and development of a validated RP-HPLC method for determination of tiagabine in presence of its degradation products. Int J Pharm Pharm Sci 2016;8:230-6.
Rao PVL, Rao A, Svum P. Development and validation of new stability indicating reversed-phase high-performance liquid chromatography method for simultaneous determination of metformin hydrochloride and ertugliflozin in bulk and pharmaceutical dosage form. Asian J Pharm Clin Res 2019;12:235-40.
Sharma S, Goyal S, Chauhan K. A review on analytical method development and validation. Int J Appl Pharm 2018;10:8-15.