Skip to main content
SpringerLink
Log in

Quantitative Estimation of 10 Known Impurities from Indacaterol Acetate, Glycopyrronium, and Mometasone Furoate Dry Powder Inhalation Product

  • Original
  • Published:
Chromatographia Aims and scope Submit manuscript

Abstract

Indacaterol, glycopyrronium, and mometasone furoate triple combination inhalable fixed-dose medicines are effectively used to treat asthma and various chronic pulmonary disorders. The study aimed to develop and validate a simple single-run RP-HPLC impurity quantitation method. The chromatographic separation was accomplished using gradient elution mode of mobile phase A (potassium dihydrogen phosphate buffer pH 2.2) and mobile phase B (mixture of acetonitrile and methanol), with a flow rate of 0.8 mL/min using YMC Triart, C18 (250 × 4.6 mm, 5 µm) HPLC column at 45 °C and the detection wavelength of 210 nm (for indacaterol, glycopyrronium and their impurities) and 248 nm (for mometasone furoate and its impurities). Water and methanol (20:80) were used as a diluent. Quantitation of 10 known and several unknown impurities was successfully performed with the determination of relative response factors for all the known impurities. The developed method was validated as per the ICH Q2(R1) guidelines. The stability indicating the nature of the method was proved by performing stress study on the sample and placebo. The linearity and range of the method were proved by calculating the r2 values (> 0.998). The overall precision was found to be within 1.82 − 7.76% RSD. The recovery for all the actives and known impurities were within 90 − 115% with 0.4 − 12% RSD. The sample solution was stable for 2 days at room temperature. The developed method can be successfully used for the impurity analysis of routine, stability, and commercial samples in a quality control laboratory of the pharmaceutical industry.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

All data and materials are available upon request.

References

  1. Vaidya S, Jauernig J, Ethell B, Abdallah N, Machineni S, Drollmann A, Heudi O, Last S, Hahn M, Radhakrishnan R, Ignatenko S, Tillmann H (2020) Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate following once-daily inhalation as a combination in healthy subjects. Pulm Pharmacol Ther 64:1–8. https://doi.org/10.1016/j.pupt.2020.101964

    Article  CAS  Google Scholar 

  2. "International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use" (2006) ICH Harmonized Tripartite Guidelines Q-3B (R2), Geneva. https://database.ich.org/sites/default/files/Q3B%28R2%29%20Guideline.pdf. Accessed 2 Jun 2006

  3. Awale PM, Patil PS, Patil SV (2021) Review on ICH guidelines in impurity profiling. Int J Creat Res Thoughts 9(7):828–845

    Google Scholar 

  4. Nath D, Sharma B (2019) Impurity profiling-a significant approach in pharmaceuticals. Curr Pharm Anal 15(7):669–680

    Article  CAS  Google Scholar 

  5. Katkade M, Baviskar A, Kotade K, Bhangale C (2023) Method development and validation of indacaterol maleate by RP-HPLC in bulk and pharmaceutical dosage form. Int J Pharm Sci 1(3):125–133. https://doi.org/10.5281/zenodo.7606967

    Article  Google Scholar 

  6. Vutukuri N, Ajitha M (2022) Stability indicating RP-HPLC method development and validation for simultaneous estimation of indacaterol and glycopyrrolate and in bulk and pharmaceutical dosage form. World J Pharm Sci 10(01):74–81. https://doi.org/10.54037/WJPS.2022.100107

    Article  CAS  Google Scholar 

  7. Ingale SL, Hingane LD, Nakhate ST (2022) Formulation and evaluation of analytical methods for determination of indacaterol. Int J Res Appl Eng Sci Technol 10:4676–4697. https://doi.org/10.22214/ijraset.2022.44995

    Article  Google Scholar 

  8. Pippalla S, Nekkalapudi AR, Jillellamudi SB (2022) Stability indicating RP-UPLC method for quantification of glycopyrrolate, methylparaben and propylparaben assay in liquid oral formulation. Am J Anal Chem 13:538–552. https://doi.org/10.4236/ajac.2022.1312036

    Article  CAS  Google Scholar 

  9. Banoth RK, Nethikoppula RL (2021) Int J Pharm Sci Res 12(7):3781–3790

    CAS  Google Scholar 

  10. Vani G, Thejomoorthy K, Prasanna PS (2021) A validated stability indicating RP-HPLC method development and validation of for simultaneous estimation of indacaterol and glycopyrrolate in pharmaceutical dosage form. Int J Pharm Drug Anal 9(2):71–79. https://doi.org/10.47957/ijpda.v9i2.464

    Article  CAS  Google Scholar 

  11. Ravi A, Chatterjee A, Sharma R, Gaur S, Shrivastava B, Kumar P (2020) Res J Pharm Technol 13(7):3093–3097

    Article  Google Scholar 

  12. Devaraj S, Sivaperuman A, Nagarajan NC (2020) Acta Pharm Sci 58(3):335–348

    CAS  Google Scholar 

  13. Kulkarni PN, Dodake-Supekar AM, Gill CH (2020) Simultaneous determination of Mometasone Furoate and Benzalkonium Chloride-A stability indicating method. Rasayan J Chem 13(3):1522–1530

    Article  CAS  Google Scholar 

  14. Salem YA, Hammouda MEA, Abu El-Enin MA, El-Ashry SM (2019) Multiple analytical methods for determination of formoterol and glycopyrronium simultaneously in their novel combined metered dose inhaler. BMC Chem 13(1):1–13

    Article  Google Scholar 

  15. Levin M, Ostanina N, Gumeniuk O, Meleshko R, Tereshchenko O, Nikolaieva Y, Brytsun V, Tarasenko N, Savina N, Kuznetsova O, Ocheretiana N, Cheremenko A, Briazkalo V, Bykov S (2019) Heliyon 5(11):1–17

    Article  Google Scholar 

  16. El-Abasawy NMA, Attia KAM, Abouserie AA, El-Olemy A, Elsayed AO (2018) Application of TLC Densitometric and UV Spectrophotometric techniques for simultaneous determination of Indacaterol and Glycopyrronium in inhalation capsules used for treatment of chronic obstructive pulmonary disease. Eur J Biomed Pharm Sci 5(5):80–89

    Google Scholar 

  17. Zayed S, Belal F (2017) Chem Cent J 11(36):1–8

    Google Scholar 

  18. Dwivedi J, Patel D, Patel K, Meshram D (2017) J Global Trends Pharm Sci 8(3):4204–4216

    Google Scholar 

  19. Dwivedi J, Patel D, Patel K, Meshram D (2017) Int J of Pharma Chem Res 3(3):447–450

    Google Scholar 

  20. Roy C, Chakrabarty J (2013) Stability-indicating validated novel RP-HPLC Method for simultaneous estimation of methylparaben, ketoconazole, and mometasone furoate in topical pharmaceutical dosage formulation. ISRN Anal Chem. https://doi.org/10.1155/2013/342794

    Article  Google Scholar 

  21. Shaikh KA, Patil AT (2013) J Trace Anal Food Drugs 1:14–21

    Google Scholar 

  22. Ourique AF, Contri RV, Guterres SS, Beck RCR, Pohimann AR, Melero A, Schaefer UF (2012) Set-up of a method using LC-UV to assay Mometasone Furoate in Pharmaceutical dosage forms. Quim Nova 35(4):818–821. https://doi.org/10.1590/S0100-40422012000400030

    Article  CAS  Google Scholar 

  23. Shaikh S, Muneera MS, Thusleem OA, Tahir M, Kondaguli AV (2009) A simple RP-HPLC method for the simultaneous quantitation of chlorocresol, mometasone furoate, and fusidic acid in creams. J Chromatogr Sci 47(2):178–183. https://doi.org/10.1093/chromsci/47.2.178

    Article  CAS  PubMed  Google Scholar 

  24. Musmade BD, Sawant AV, Kulkarni SV, Nage SD, Bhope SG, Padmanabhan S, Lohar KS (2022) Method development, validation and estimation of relative response factor for the quantification of known impurities in mometasone furoate nasal spray dosage form by RP-HPLC with UV/PDA detector. Pharm Chem J 56(4):538–544. https://doi.org/10.1007/s11094-022-02672-5

    Article  CAS  Google Scholar 

  25. Chawla RK, Rao GSNK, Kulandaivelu U, Panda SP, Alavala RR (2021) A selective and sensitive method development and validation of 1,1-dimethyl-3-hydroxy-pyrrolidinium bromide impurity in glycopyrrolate oral solution by liquid chromatography. J Chromatogr Sci 59(6):566–575. https://doi.org/10.1093/chromsci/bmab003

    Article  CAS  PubMed  Google Scholar 

  26. Soliman SM, EL-Houssini OM, (2019) HPTLC method for determination of r, r-glycopyrronium bromide and its related impurities. J Chromatogr Sci 57(9):799–805. https://doi.org/10.1093/chromsci/bmz055

    Article  CAS  PubMed  Google Scholar 

  27. Zuo L, Zhao Y, Ji F, Zhao M, Jiang Z, Sun T, Guo X (2014) Determination of the enantiomeric and diastereomeric impurities of RS-glycopyrrolate by capillary electrophoresis using sulfated-β-cyclodextrin as chiral selectors. Electrophor 35(23):3339–3344. https://doi.org/10.1002/elps.201400170

    Article  CAS  Google Scholar 

  28. Sharma N, Rao SS, Vaghela B (2013) Indian J Pharm Sci 75(1):76–82

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nebiu D, Walter M, Lachmann B, Kopelent H, Noe CR (2007) Pharmazie 62(6):406–410

    CAS  PubMed  Google Scholar 

  30. "International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use” (2005) ICH Harmonized Tripartite Guidelines Q2(R1), Geneva. https://database.ich.org/sites/default/files/Q2%28R1%29%20Guideline.pdf. Accessed Nov 2005

Download references

Acknowledgements

The authors are thankful to Mr. Vinod Ramachandra Jadhav, Chairman and Mr. Dinesh Kapoor, Managing Director Sava Healthcare Ltd. for their support and encouragement.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Sava Healthcare Limited, Research Centre, Block D1, Plot No. 17/6, MIDC, Chinchwad, Pune, 411019, India

    Shrikant V. Kulkarni, Pushpavati R. Zinjad, Shrinivas G. Bhope & Mitesh Nagar

  2. Department of Chemistry, K. M. C. College Khopoli, Raigad, MS, 410203, India

    Sharad P. Panchgalle

  3. Department of Chemistry, Kai. Rasika Mahavidyalaya Deoni, Latur, MS, 413519, India

    Vijaykumar S. More

Authors
  1. Shrikant V. Kulkarni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pushpavati R. Zinjad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shrinivas G. Bhope
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mitesh Nagar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sharad P. Panchgalle
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vijaykumar S. More
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Study conception and design by [Vijaykumar More] and [Mitesh Nagar]. Material collection, experimental analysis, data collection and interpretation were performed by [Shrikant Kulkarni], [Pushpavati Zinjad], [Shrinivas Bhope] and [Sharad Panchgalle]. The first draft of the manuscript was written by [Shrikant Kulkarni] and [Shrinivas Bhope]. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Vijaykumar S. More.

Ethics declarations

Competing interests

Authors are declaring no financial or non-financial interests to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kulkarni, S.V., Zinjad, P.R., Bhope, S.G. et al. Quantitative Estimation of 10 Known Impurities from Indacaterol Acetate, Glycopyrronium, and Mometasone Furoate Dry Powder Inhalation Product. Chromatographia (2024). https://doi.org/10.1007/s10337-024-04339-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10337-024-04339-7

Keywords

Search

Navigation