STABILITY-INDICATING REVERSED-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR ANALYZING INJECTION DOSAGE FORMULATION CONTAINING MEDROXYPROGESTERONE ACETATE AND ESTRADIOL CYPIONATE
Objective: Stability-indicating reversed-phase high-performance liquid chromatography method with photodiode array detection is described for the assay of medroxyprogesterone acetate (MDA) and estradiol cypionate (ECA) in bulk and injection dosage form.
Methods: MDA and ECA were determined on a Cosmicsil (250 mm × 4 mm) C18, 5 μm analytical column using mobile phase of 0.1 M KH2PO4 and acetonitrile (65:35 v/v) supplied isocratically by a flow rate of 1 ml/min. During stress testing, the sample was subjected to stress with 0.1 N HCl, 0.1 N NaOH, 30% hydrogen peroxide, water, and 105°C in oven and sunlight. Method validation was done in accordance with international conference on harmonization.
Results: The linear response was obtained over the concentration range from 2.5 to 7.5 μg/ml for ECA and 12.5 to 37.50 μg/ml for MDA. The recoveries of MDA and ECA were 99.31%–99.45% and 99.59%–99.79%, with relative standard deviation ranging from 0.021% to 0.217% and 0.027% to 0.187%, respectively. The limits of detection for MDA and ECA were 0.097 μg/ml and 0.042 μg/ml, respectively. The method was able to selectively quantitate MDA and ECA in the presence of the degradation products and, hence, can be considered as stability-indicating one. Proposed method was applied to the quantification of MDA and ECA in injection dosage form with good precision and accuracy.
Conclusion: The method can be employed for routine and quality control analysis of MDA and ECA simultaneously.
2. Medroxyprogesterone (By Mouth); 2018. Available from: https://www. ncbi.nlm.nih.gov/pubmedhealth/PMHT0011057/?report= details.
3. Haiyan G, Yun W, Qiuju C, Weiran C, Lihua S, Ai A, et al. Use of medroxyprogesterone acetate in women with ovarian endometriosis undergoing controlled ovarian hyper stimulation for in vitro fertilization. Sci Rep 2017;7:11927.
4. Kuang Y, Chen Q, Fu Y, Wang Y, Hong Q, Lyu Q, et al. Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Fertil Steril 2015;104:62-70000.
5. Michael O, Ekkehard S. Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen. Heidelberg: Springer Science and Business Media; 2012. p. 261.
6. Kuhl H. Pharmacology of estrogens and progestogens: Influence of different routes of administration. Climacteric 2005;8 Suppl 1:3-63.
7. Farooq A. Structural and functional diversity of estrogen receptor ligands. Curr Top Med Chem 2015;15:1372-84.
8. Santoro N, Epperson CN, Mathews SB. Menopausal symptoms and their management. Endocrinol Metab Clin North Am 2015;44:497-515.
9. Lunelle™ Monthly Contraceptive Injection-FDA. Available from: https:// www.accessdata.fda.gov/drugsatfda_docs/label/2000/20874lbl.pdf.
10. Thurman A, Kimble T, Hall P, Schwartz JL, Archer DF. Medroxyprogesterone acetate and estradiol cypionate injectable suspension (Cyclofem) monthly contraceptive injection: Steady-state pharmacokinetics. Contraception 2013;87:738-43.
11. Sierra-Ramírez JA, Lara-Ricalde R, Lujan M, Velázquez-Ramírez N, Godínez-Victoria M, Hernádez-Munguía IA, et al. Comparative pharmacokinetics and pharmacodynamics after subcutaneous and intramuscular administration of medroxyprogesterone acetate (25 mg) and estradiol cypionate (5 mg). Contraception 2011; 84:565-70.
12. Shulman LP. Contraception 2000: Lunelle, an injectable combination contraceptive option. J Womens Health Gend Based Med 2000;9:725 9.
13. Sankar M, Arulantony S, Gunshekhar R, Kumar KV. Compatibility method validation of medroxyprogesterone acetate and estradiol cypionate combination drug in injectable suspension dosage forms. AmJ Pharm Health Res 2014;2:9.
14. Kats M. Forced Degradation Studies: Regulatory Considerations and Implementation. Bio Pharm Int 2005. Available from: http://www. biopharminternational.com/forced-degradation-studies-regulatory-considerations-and-implementation.
15. John WD. Stability indicating assay: LC troubleshooting. LCGC North Am 2002;20:346-9.
16. International Conference Harmonization (ICH). Topic Q1A (R2) Stability Testing of New Drug Substances and Products. Geneva: IFPMA; 2003.
17. International Conference Harmonization (ICH). Topic Q2 (R1) Validation of Analytical Procedure: Test and Methodology. Geneva: IFPMA; 2005.
18. Bhavani T, Susmita AG, Rajitha G. Method development, validation and stability studies for the determination of lurasidone hydrochloride in bulk and tablet dosage form by RP-HPLC. Int J Pharm Pharm Sci 2018; 10:58-63.
19. Gorja A, Sumanta M. Stability indicating method development and validation for the estimation of panobinostat lactatein pharmaceutical dosage forms by UPLC. Int J Pharm Pharm Sci 2018;11:60-5.
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