• SANATHOIBA SINGHA S Rahman Institute of Pharmaceutical Sciences and Research, Guwahati, Assam, India.
  • SREENIVAS RAO T Department of Pharmaceutical Analysis, Karnataka College of Pharmacy, Bengaluru, Karnataka, India.


Objective: This work makes an attempt to establish a sensitive and accurate method for the development and validation of an analytical method for estimation of ulipristal acetate (UPA) in bulk and pharmaceutical dosage form.

Methods: A mixture of 20 mM acetate buffer pH 3.7 and methanol in the ratio of 70:30 (v/v %) was used as the mobile phase. An xBridge™ C18 column (250 mm × 4.6 mm, 5μ) was used for the analysis at a flow rate of 1 ml/min, injection volume of 20 μl, run time of 15 min, and detection wavelength of 309 nm. The repeatability (within-day in triplicates) and intermediate precision (for 2 days) were carried out by six injections and the obtained results within and between the days of trials were expressed as percent relative standard deviation (% RSD). The linearity of the method was determined by the analysis of analyte concentration across a range of 10 μg/ml–60 μg/ml.

Results: The % RSD values of precision studies were found to be below the accepted limit of 2%. The method was found to be linear with a correlation coefficient (R2) of 0.98. The method was also found to be accurate and robust with suitable values. Limit of detection (LOD) and limit of quantification (LOQ) of the method were found to be 0.371 μg/ml and 1.23 μg/ml, respectively.

Conclusion: The results of analysis prove that this method can be used for the routine determination of UPA in bulk drug and in pharmaceutical dosage forms.

Keywords: Contraceptive, HPLC, Methanol, Signal to noise ratio, Ulipristal acetate, Uterine fibroids


1. Hoellen F, Griesinger G, Bohlmann MK. Therapeutic drugs in the treatment of symptomatic uterine fibroids. Expert Opin Pharmacother 2013;14:2079-85.
2. Buttram VC Jr., Reiter RC. Uterine leiomyomata: Etiology, symptomatology, and management. Fertil Steril 1981;36:433-45.
3. Rein MS, Friedman AJ, Barbieri RL, Pavelka K, Fletcher JA, Morton CC. Cytogenetic abnormalities in uterine leiomyomata. Obstet Gynecol 1991;77:923-6.
4. Mashal RD, Fejzo ML, Friedman AJ, Mitchner N, Nowak RA, Rein MS, et al. Analysis of androgen receptor DNA reveals the independent clonal origins of uterine leiomyomata and the secondary nature of cytogenetic aberrations in the development of leiomyomata. Genes Chromosomes Cancer 1994;11:1-6.
5. Ligon A, Morton C. Leiomyomata: Heritability and cytogenetic studies. Hum Reprod Update 2001;7:8-14.
6. Baird DD, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterine leiomyoma in black and white women: Ultrasound evidence. Am J Ostet Gynecol 2003;188:100-7.
7. Philipp CS, Faiz A, Heit JA, Kouides PA, Lukes A, Stein SF, et al. Evaluation of a screening tool for bleeding disorders in a US multisite cohort of women with menorrhagia. Am J Obstet Gynecol 2011;204:209.
8. Zakherah MS, Sayed GH, El-Nashar SA, Shaaban MM. Pictorial blood loss assessment chart in the evaluation of heavy menstrual bleeding:Diagnostic accuracy compared to alkaline hematin. Gynecol Obstet Invest 2011;71:281-4.
9. Melis GB, Piras B, Marotto MF, Orru MM, Maricosu G, Pilloni M, et al. Pharmacokinetic evaluation of ulipristal acetate for uterine leiomyoma treatment. Expert Opin Drug Metab Toxicol 2012;8:901-8.
10. Donnez J, Jadoul P. What are the implications of myomas on fertility? A need for a debate? Hum Reprod 2002;17:1424-30.
11. Practice Committee of American Society for Reproductive Medicine in Collaboration with Society of Reproductive Surgeons. Myomas and reproductive function. Fertil Steril 2008;90:S125-30.
12. Donnez J, Jadoul P. What are the implications of myomas on fertility? A need for a debate? Hum Reprod 2002;17:1424-30.
13. Tafi E, Scala C, Maggiore UL, Bizzarri N, Candiani M, Venturini PL, et al. Drug safety evaluation of ulipristal acetate in the treatment of uterine fibroids. Expert Opin Drug Saf 2015;14:965-77.
14. McCarthy-Keith DM, Armstrong AY. Innovations in uterine fibroid therapy. Therapy 2011;8:189-200.
15. Talaulikar VS, Belli AM, Manyonda I. GnRH agonists: Do they have a place in the modern management of fibroid disease? J Obstet Gynecol India 2012;62:506-10.
16. Chwalisz K, Perez MC, DeManno D, Winkel C, Schubert G, Elger W. Selective progesterone receptor modulator development and use in the treatment of leiomyomata and endometriosis. Endocr Rev 2005;26:423-38.
17. Gainer EE, Ulmann A. Pharmacologic properties of CDB(VA)-2914. Steroids 2003;68:1005-11.
18. Horak P, Mara M, Dundr P, Kubinova K, Kuzel D, Hudecek R, et al. Effect of a selective progesterone receptor modulator on induction of apoptosis in uterine fibroids in vivo. Int J Endocrinol 2012;2012:436174.
19. Pohl O, Osterloh I, Gotteland JP. Ulipristal acetate - safety and pharmacokinetics following multiple doses of 10-50 mg per day. J Clin Pharm Ther 2013;38:314-20.
20. Donnez J, Tatarchuk TF, Bouchard P, Puscasiu L, Zakharenko NF, Ivanova T, et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med 2012;366:409-20.
21. Biglia N, Carinelli S, Maiorana A, D’Alonzo M, Lo Monte G, Marci R. Ulipristal acetate: A novel pharmacological approach for the treatment of uterine fibroids. Drug Des Dev Ther 2014;8:285-92.
22. Chabbert-Buffet N, Meduri P, Bouchard G, Spitz IM. Selective progesterone receptor modulators and progesterone antagonists: Mechanisms of action and clinical applications. Hum Reprod Update 2005;11:293-307.
23. Goyeneche AA, Seidel EE, Telleria CM. Growth inhibition induced by antiprogestins RU-38486, ORG-31710, and CDB-2914 in ovarian cancer cells involves inhibition of cyclin dependent kinase 2. Invest New Drugs 2012;30:967-80.
24. Chabbert-Buffet N, Ouzounian S, Kairis A, Bouchard P. Contraceptive applications of progesterone receptor modulators. Eur J Contracept Reprod Health Care 2008;13:222-30.
25. Cunningham F, Leveno K, Bloom S, Hauth J, Rouse D, Spong C. Williams Obstetrics. Vol. 23. New York: McGraw-Hill Professional; 2010. p. 692-4.
26. Emma H. FDA Panel Gives UPA Unanimous Positive Vote for Emergency Contraception Indication. New York: Medscape Medical News; 2010. Available from: viewarticle/723822. [Last accessed on 2020 Feb 03].
27. Richardson AR, Maltz FN. Ulipristal acetate: Review of the efficacy and safety of a newly approved agent for emergency contraception. Clin Ther 2011;34:24-36.
28. National Center for Biotechnology Information. PubChem Compound Summary for CID 130904, UPA. Available from: https://www.pubchem. [Last accessed on 2020 Feb 05].
29. Ulipristal, Drug Bank. Available from: DB08867. [Last accessed on 2020 Feb 05].
30. ERA Consulting. AusPAR Attachment 1: Product Information for UPA. Available from: is%20a%20white,ethanol%20and%20insoluble%20in%20water. [Last accessed on 2020 Feb 05].
31. Jin-Xiao S, Feng-Yan Z, Qiao-Gen Z, Li-Ii S, Ping W. Determination of UPA and its related substances by HPLC. Chin J New Drugs 2014;7:839-42.
32. Rao AL, Alimunnisa, Tejaswini DS, Lakshmi GLVJ, Vani VBN. Development and validation of stability indicating HPLC method for the determination of UPA in pharmaceutical dosage form. Int J Res Ayush Pharm Sci 2019;3:321-7.
33. Validation of Analytical Procedures: Text and Methodology Q2(R1). International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Available from: Guideline.pdf. [Last accessed on 2020 Feb 08].
34. Narasimhan B, Abida K, Srinivas K. Stability indicating RP-HPLC method development and validation for oseltamivir API. Chem Pharm Bull 2008;56:413-7.
35. Sreekanth N, Rao CB, Mukkanti K. RP-HPLC method development and validation of ropinirole hydrochloride in bulk and pharmaceutical dosage forms. Int J Pharm Pharm Sci 2009;1:186-92.
36. Swamy GK, Rao JV, Kumar JM, Kumar UA, Bikshapathi DV, Kumar DV. Analytical method development and validation of aliskiren in bulk and tablet dosage form by RP- HPLC method. J Pharm Res 2011;4:865-7.
37. Debata J, Kumar S, Jha SK, Khan A. A new RP-HPLC method development and validation of dapagliflozin in bulk and tablet dosage form. Int J Drug Dev Res 2017;9:48-51.
38. Çelebier M, Reçber T, Koçak E, Alt?nöz S. RP-HPLC method development and validation for estimation of rivaroxaban in pharmaceutical dosage forms. Braz J Pharm Sci 2013;49:359-66.
25 Views | 21 Downloads
How to Cite
SINGHA S, S., and S. RAO T. “DEVELOPMENT AND VALIDATION OF AN RP-HPLC METHOD FOR THE DETERMINATION OF ULIPRISTAL ACETATE IN BULK AND PHARMACEUTICAL DOSAGE FORM”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 14, no. 4, Apr. 2021, pp. 83-89, doi:10.22159/ajpcr.2021.v14i4.40631.
Original Article(s)