Doripenem (DM), an antibiotic used for kidney, lung, and urinary infections, underwent the development of a robust high-performance liquid chromatography (HPLC) technique using the quality-by-design approach. This method, integrating design-of-experiments, detected organic impurities in both drug substances and formulated products. Operating with a C18 analytical column in a binary gradient mode with potassium phosphate buffer (pH 6.1) and acetonitrile as mobile phases, the method ran at a flow rate of 1.20 ml/minutes, with an injection volume of 20-μl and a column temperature of 45°C. Stability testing under various conditions, including hydrolysis, oxidation, heat, humidity, and light exposure, confirmed the method’s reliability without interference. Validation studies, compliant with ICH guidelines, revealed quantitation limits of 0.006%, linearity between 0.060 and 1.800 μg/ml (R2 > 0.999), and recoveries ranging from 96.8% to 99.1%. This HPLC method was effectively used for stability assessment in quality control testing, assessing doripenemic acid, doripenem assay, and organic impurities.
Boppy NVVDP, Haridasyam SB, Vadagam N, Sara N, Sara K, Tamma E. Stability-indicating HPLC method optimization using quality by design with design of experiments approach for quantitative estimation of organic related impurities of Doripenem in pharmaceutical formulations. J Appl Pharm Sci. 2024. Online First. http://doi.org/10.7324/JAPS.2024.190386
1. Doribax (doripenem) injection IV label, 2007 [cited 2023 June 20]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022106s008lbl.pdf
2. Narasimha SL, Chandrasekar K, Niroja V, Poornima R, Kalyani C, Sanjeeva RC. Molecular docking, in-vitro anticancer evaluation and ADME profiling of 7-Oxo Midostaurin. J Mole Struct. 2023;1293:136159. doi: https://doi.org/10.1016/j.molstruc.2023.136159
3. ICH. Q3A(R2), Impurities in new drug substances, 2006 [cited 2023 July 20]. Available from: https://database.ich.org/sites/default/files/Q3A%28R2%29%20Guideline.pdf
4. ICH. Q3B(R2), Impurities in new drug products, 2006 [cited 2023 July 20]. Available from: https://database.ich.org/sites/default/files/Q3B%28R2%29%20Guideline.pdf
5. Vadagam N, Haridasyam SB, Venkatanarayana M. Stability-indicating normal-phase HPLC method development for separation and quantitative estimation of S-enantiomer of lacosamide in pharmaceutical drug substance and tablet dosage form. Biomed Chromatogr. 2023;37(9):e5688. doi: https://doi.org/10.1002/bmc.5688
6. Vadagam N, Haridasyam SB, Venkatanarayana M, Lakka NS, Chinnakadoori SR. Separation and quantitative estimation of stereo-selective enantiomers of montelukast in pharmaceutical drug substance and tablets dosage forms by using stability-indicating normal phase-HPLC method. Chirality. 2023;35(12):952–65. doi: https://doi.org/10.1002/chir.23610
7. Vadagam N, Haridasyam SB, Venkatanarayana M, Lakka NS, Chinnakadoori SR. Separation and quantitation of Valacyclovir Enantiomers using stability-indicating chiral liquid chromatography method with an immobilized chiral phase of Amylose Tris-(3,5-dimethylphenylcarbamate). Sep Sci Plus. 2023;6(12):2300145. doi: https://doi.org/10.1002/sscp.202300145
8. Vadagam N, Haridasyam SB, Venkatanarayana M, Lakka NS, Chinnakadoori SR. Separation and simultaneous estimation of enantiomers and diastereomers of muscarinic receptor antagonist Solifenacin using stability-indicating normal-phase HPLC technique with chiral stationary phase amylose tris-(3,5-dimethylphenylcarbamate). Chirality. 2023;36(2):e23632. doi: https://doi.org/10.1002/chir.23632
9. Lakka NS, Goswami N. A stability indicating RP-HPLC method for simultaneous determination of halobetasol propionate and pchlorocresol in creams. Int Res J Pharm Appl Sci. 2012;2(5):13–9. Available from: https://www.scienztech.org/index.php/irjpas/article/view/335
10. Praveen BNVVD, Sharath BH, Niroja V, Mohan P, Muvvala V, Belquis B. Stability-indicating liquid chromatography method development for assay and impurity profiling of amitriptyline hydrochloride in tablet dosage form and forced degradation study. Biomed Chromatogr. 2022;36(10):e5436. doi: https://doi.org/10.1002/bmc.5436
11. Narasimha SL, Nishant G, Penugonda B, Vaddi S. Development and validation of a stability-indicating RP-HPLC for the simultaneous determination of atorvastatin calcium and simvastatin in pharmaceutical solid dosage forms. Int J Res Pharm Sci. 2011;2(4):608–15.
12. Lakkireddy P, Malipeddi H, Venkata BS, Narasimha SL. Impurity profiling and a stability-indicating UPLC method development and validation for the estimation of related impurities of halobetasol propionate in halobetasol propionate 0.05% (w/w) cream. Journal of Chromatogr Sci. 2015;53(1):112–21. doi: https://doi.org/10.1093/chromsci/bmu027
13. Menda J, Chintala V, Kowtharapu LP, Kanuparthy PR, Katari NK. Quality by design tool evaluated green stability-indicating UPLC content determination method for the olanzapine and samidorphan dosage form. Microchem J. 2023;197:109835. doi: http://dx.doi.org/10.2139/ssrn.4575839
14. Nagulancha BR, Lakka NS, Vandavasi KR. Stability-indicating method development and validation for quantitative estimation of assay and organic impurities of antiviral drug baloxavir marboxil in drug substance and pharmaceutical dosage form using HPLC and LC–MS methods. Biomed Chromatogr. 2023;37(8):e5644. doi: https://doi.org/10.1002/bmc.5644
15. Vaishnavi C. Stability indicating reversed-phase-high-performance liquid chromatography method development and validation for pyridostigmine bromide and sodium benzoate in oral solution. Biomed Chromatogr. 2023;30(3):e5800. doi: https://doi.org/10.1002/bmc.5800
16. Singaram K, Garikapati D. A validated new gradient stability-indicating LC method for the analysis of Doripenem in bulk and injection formulation. Chromatogr Res Int. 2013;963595:1–9. doi: https://doi.org/10.1155/2013/963595
17. Veldi V, Golkonda R, Chintala R. A novel validated and stability indicating RP-HPLC method for the determination of doripenem in bulk and pharmaceutical formulations. Anal Chem Indian J. 2013;12(10):384–92.
18. Srinivasa RC, Vaishnavi C, Vishnu N, Rajyalakshmi C, Sasikiran GE, Leela PK, et al. Quantification of Drospirenone- and ethinyl estradiol-related impurities in a combined pharmaceutical dosage form by a chromatography method with a QbD Robustness study. J AOAC Int. 2023;107(1):31–9. doi: https://doi.org/10.1093/jaoacint/qsad118
19. Jose K, Jayasekhar P. Stability indicating HPLC determination of Doripenem in pharmaceutical dosage forms. Int J Pharm Sci Rev Res. 2013;22(2):41–5.
20. Paliosa PK, Garcia CV, Schapoval EES, Mendez ASL. Quantitative determination of the β-methyl carbapenem doripenem in powder for injection by a stability-indicating capillary zone electrophoresis method. Die Pharm Int J Pharm Sci. 2015;70(9):569–73. doi: https://doi.org/10.1691/ph.2015.5008
21. Katarzyna M, Genowefa P, Stefan T. Determination of doripenem and related substances in medicinal product using capillary electrophoresis. J Sep Sci. 2011;34(4):475–82. doi: https://doi.org/10.1002/jssc.201000504
22. Andreas SLM, Luciano M, Fábio B, Carla TMS, Cássia VG, Fávero RP, et al. Characterization of the antibiotic Doripenem using physicochemical methods-chromatography, spectrophotometry, spectroscopy and thermal analysis. Quím Nova. 2011;34(9):1634–8. doi: https://doi.org/10.1590/S0100-40422011000900024
23. Rajesh K, Vaishnavi C, Satya Sree N, Naresh KK, Suresh S, Murty JNSRC, et al. Isolation and identification of forced degradation products of Februxostat. 2023;1. doi: https://doi.org/10.21203/rs.3.rs-3176547/v1
24. Lakka NS, Kuppan C, Vadagam N, Reddamoni SY, Muthusamy C. Degradation pathways and impurity profiling of the anticancer drug apalutamide by HPLC and LC–MS/MS and separation of impurities using design of experiments. Biomed Chromatogra. 2022;37(2):e5549. doi: https://doi.org/10.1002/bmc.5549
25. ICH, Q2(R1). Validation of analytical procedures: text and methodology, 1996 and 2005. Available from: https://database.ich.org/sites/default/files/Q2%28R1%29%20Guideline.pdf
26. United States Pharmacopeia, USP<1225> Validation of compendia procedures, 2020. Available from: http://www.uspbpep.com/usp32/pub/data/v32270/usp32nf27s0_c1225.html
27. Narasimha SL, Kuppan C. Principles of chromatography method development. In: Boldura O-M, Baltla C, Awwad NS, editors. Biochemical analysis tools-methods for bio-molecules studies. London, UK: IntechOpen; 2019. doi. 10.5772/intechopen.89501
28. Blessy M, Ruchi DP, Prajesh NP, Agrawal YK. Development of forced degradation and stability indicating studies of drugs-a review. J Pharm Anal. 2014;4(3):159–65. doi: https://doi.org/10.1016/j.jpha.2013.09.003
29. Mohan P, Sharath BH, Niroja V, Praveen BNVVD, Sanjeeva RC, Narasimha SL. Separation and quantification of organic-related impurities of beta-adrenergic receptor blocking agent propranolol in pharmaceutical solid dosage forms: impurity profiling using stability-indicating HPLC method. Sep Sci Plus. 2023;7(1):2300159. doi: https://doi.org/10.1002/sscp.202300159
30. ICH. Q1B(R2). Stability testing: Photostability testing of new drug substances and products; 1996. Available from: https://database.ich.org/sites/sdefault/files/Q1B%20Guideline.pdf
31. ICH. Q1A (R2). Stability testing of new drug substances and products. 2003.
32. Snyder LR, Joseph JK, Joseph LG. Practical HPLC method development, 2nd ed., Hoboken, NJ: John Wiley and Sons; 2010.
33. Lakshmi NRK, Thirupathi D, Santhosh KE. Quality by design with design of experiments approach for development of a stability-indicating LC method for enzalutamide and its impurities in soft gel dosage formulation. Biomed Chromatogr. 2021;35(5):e5062. doi: https://doi.org/10.1002/bmc.5062
34. Siva KM, Naresh KK, Kalyan KS, Henele S, Vishnu MM, Santhosh KE, et al. Implementation of analytical quality by design and green chemistry principles to develop an ultra-high performance liquid chromatography method for the determination of Fluocinolone Acetonide impurities from its drug substance and topical oil formulations. J Chromatogr A. 2022;1679:463380. doi: https://doi.org/10.1016/j.chroma.2022.463380
35. Jyothsna M, Phani RK, Naresh KK, Leela PK, Santhosh KE, Surya PRP. Quality by design tool–evaluated stability-indicating ultra-performance liquid chromatography method for the determination of drugs (ritonavir and darunavir) used to treat the human immunodeficiency virus/acquired immunodeficiency syndrome. Biomed Chromatogra. 2023;37(9):e5687. doi: https://doi.org/10.1002/bmc.5687
36. Boppy N, Haridasyam, SB, Vadagam N, Venkatanarayana M, Chinnakadoori SR, Lakka NS. Separation and quantification of organic-related impurities of anti-histamine drug hydroxyzine in pharmaceutical dosage forms using stability-indicating high-performance liquid chromatography, liquid chromatography-mass spectrometry, and high-resolution mass spectrometry techniques. Sep Sci Plus. 2024; e2300157. doi: https://doi.org/10.1002/sscp.202300157
Year
Month