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Volume: 9, Issue: 2, February, 2019
RP-HPLC method for determination of norethindrone in dissolution media and application to study release from a controlled release nanoparticulate liquid medicated formulationAuthor Affiliations
Several methods are available for the determination of norethindrone. These methods are either complicated or need validation. The objective of this work was to develop and validate a simple reversed phase-high performance liquid chromatographic method for the determination of norethindrone in dissolution media. A Thermo Scientific C18 column (250 mm × 4.6 mm ID, 5 µm pore size) was used. A mobile phase consisting of deionized water: acetonitrile (50:50, v/v) and 5 ml/l acetic acid was used. The flow rate was 1.3 ml/minute and the wavelength of the detection was 245 nm. Validation of linearity, accuracy and precision, limit of detection, limit of quantification, specificity, and stability (degradation) was carried out according to the International Conference on Harmonization guidelines. The developed and validated method was used to study norethindrone release from a nanoparticulate liquid medicated formulation (LMF). The results indicated that the method was simple, accurate and precise, and met the acceptance criteria. The drug exhibited higher stability in basic media when compared to acidic media. Drug release from a LMF (nanoemulsion) followed zero order kinetics. In conclusion, a simple method was developed, validated, and used successfully in evaluating in vitro drug release from a sustained release/controlled release nanoparticulate LMF.
Copyright: The Author(s). This is an open access article distributed under the Creative Commons Attribution Non-Commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ajitha K, Kimbahune R, Mubeen G, Lalitha N, Chakraborty K. Reversed-phase high-performance liquid chromatographic determination of norethindrone acetate and ethinyl estradiol in pharmaceutical formulation. Indo Am J Pharm Res, 2015; 2231-6876:2242-2249.
Ajitha K, Kimbahune R, Mubeen G, Pai Y. Simultaneous spectrophotometric estimation of norethindrone acetate and ethinyl estradiol in formulation. Anal Chem Ind J, 2016; 16:156-162.
Analytical Best Practices, Establishing acceptance criteria for analytical methods, October 2016. www.biopharminternational.com acessed on 1/10/2018
Bansal K, Pant P, Rama Therdana Rao P, Venkateswar Reddy M, Padhee K, Sathapathy A, Kochhar PS. UV spectrophotometric method for the estimation of norethindrone in immediate release tablet. Int J Pharm Sci Drug Res, 2011; 3:127-129.
Food, Drug Administration Centre for Drug Evaluation and Research (FDA). Guidance for Industry-Bioanalytical Method Validation, Center for Drug Evaluation and Research, US Department for Health and Human Services, Silver Spring, MD, 2013 (May 2001).
Goeh TJ, Sundaresan GM,Prasad VK. Analytical methodology applicable in dissolution of norethindrone-mestranol. Int J Pharm, 1982; 11:181-186. https://doi.org/10.1016/0378-5173(82)90036-9
Hashem H, Abd El-Hay S, Jira T. A rapid stability indicating HPLC-method for determination of norethisterone acetate in plasma, tablets and in a mixture with other steroids. Int J Pharm Pharmaceut Sci, 2015; 7:279-282.
Hirai S, Hussain A, Babhair S. Sensitive method for determination of ethinyl estradiol in presence of norethindrone. J Pharm Sci, 1980; 69:857-9. doi.org/10.1002/jps.2600690732. https://doi.org/10.1002/jps.2600690732
Krishna PM, Rao BT, R. Kumar K, Venkateswarlu P. Development and validation of method for the determination of related substances of norethindrone in norethindrone tablets and degradation studies. Int J ChemTech Res, 2011; 3:143-148.
Rao R, Talluri MV, Raju AN, Shinde DD, Ramanjaneyulu GS. Development of a validated RP-LC/ESI-MS–MS method for separation, identification and determination of related substances of tamsulosin in bulk drugs and formulations. J Pharm Biomed Anal, 2008; 46:94-103.doi.org/10.1016/j.jpba.2007.09.009
Reddy L. S, Reddy S. L. N. P, Reddy G. S. Development and Validation of a Stability Indicating Liquid Chromatographic Method for Simultaneous Estimation of Dutasteride and Tamsulosin in Combined Dosage Form. Orient J Chem, 2013; 29(4). Available from: http://www.orientjchem.org/?p=1075
Santos M, Hendry D, Sangi-Haghpeykar H, Dietrich JE. Retrospective review of norethindrone use in adolescents. J PediatrAdolesc Gynecol, 2014; 27:41-44. doi: 10.1016/j.jpag.2013.09.002. https://doi.org/10.1016/j.jpag.2013.09.002
Schindler AE,Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH.Classification and pharmacology of progestins. Maturitas, 2003;46 Supp:S7-S16. https://doi.org/10.1016/j.maturitas.2003.09.014
Suresh R, Anarthanan S, Manavalan R, Valliappan K. Aspects of validation in HPLC method development for pharmaceutical analysis - Comparison of validation requirements by FDA, USA and ICH. Int J Pharm Sci Res, 2010; 12:123-133. doi.org/10.13040/IJPSR.0975-8232.1(12).123-32. https://doi.org/10.13040/IJPSR.0975-8232.1(12).123-32
Tiwari G, Tiwari R. Bioanalytical method validation: An updated review. Pharm Methods, 2010;1(1):25–38. doi: 10.4103/2229-4708.72226 https://doi.org/10.4103/2229-4708.72226
2017. Available at: https://www.drugs.com/pro/norethindrone-tablets.html/[accessed 25 March 2017].
Lo’pez de Alda MJ, Barcelo D. Determination of steroid sex hormones and related synthetic compounds considered as endocrine disrupters in water by liquid chromatography–diode array detection–mass spectrometry. JChromatogrA,2000;892:391–406. https://doi.org/10.1016/S0021-9673(00)00068-6
Lindholm J. Development and validation of HPLC methods for analytical and preparative purposes. Uppsala,Sweden: Acta Universitatis Upsaliensis, 2004 (dissertation).
Validation of analytical procedures: text and methdology Q2_R1__guideline. International Conference of Harmonization of Technical Requierments for Regstarion of Phrmacuticals for Human Use. ICH Harmonized Tripartite Guidline. Parent Guideline dated 27 October 1994.
Validation of Compendial Procedures. USP30-NF25, 2008.
Venkateswarlu K, Rangareddy A, Narasimhaiah K, Sharma H, Mallikarjuna N, Bandi R. A validated stability indicating RP-HPLC method for estimation of Armodafinil in pharmaceutical dosage forms and characterization of its base hydrolytic product. Pak J Pharm Sci, 2017;30(1):23-28.