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Advancing Quality and Environmental Responsibility: A Stability-Indicating LC Method Development for Lenvatinib Through QbD and Green Chemistry

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Abstract

A Quality by Design (QbD) systematic and analytical approach was used  to develop a novel and sensitive Lenvatinib stability-indicating method. The ICH Q1A(R2) and Q3 guidelines were implemented to determine Lenvatinib degradation behavior under various environmental conditions. The QbD approach implementation has  screening and optimization stages.The Placket–Burman design was used to assess primary parameters, and Response Surface Design (RSD) to optimize critical factors. The drug degradation was examined under different degradation conditions, including acidic, basic, oxidative, neutral, thermal, and photolytic conditions. Separation was achieved using a Shimadzu® C18 column (250 mm × 4.6 mm, particle size 5 µ) with the mobile phase consisted of Acetonitrile: 10 mM ammonium acetate at pH 3.5 (39:61, v/v) at a flow rate 0.8 mL/min. The run time was 20 min and the wavelength used was 245 nm. The drug found sensitive toward acid and base hydrolysis, resulting in the generation of  five degradation products. These products were successfully identified using the optimized LC–MS compatible analytical method. The optimized method was found to be sensitive, reproducible, specific, and robust, with a linearity range of 10 to 60 mg/mL and a correlation coefficient (R2 = 0.9993). The greenness score of the analytical method was calculated, revealing that the developed method is  environmentally friendly.

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Data Availability

All the data generated or analyzed during this study are included in this published article and as in form of supplementary data.

Abbreviations

nm:

Nanometer

ppm:

Parts per million

°C:

Degree Celsius

mL:

Milliliter

µg:

Micron gram

SIAM:

Stability-indicating assay method

mg:

Milligram

Conc.:

Concentration

HPLC:

High-Performance Liquid Chromatography

LC/MS–MS:

Liquid Chromatography–Mass Spectrometry

HCl:

Hydrochloric acid

NaOH:

Sodium Hydroxide

MeOH:

Methanol

ACN:

Acetonitrile

pH:

Potential of Hydrogen

Hrs:

Hours

min:

Minute

DOE:

Design of Experiment

QbD:

Quality by Design

H2O2 :

Hydrogen peroxide

PBD:

Plackett–Burman Design

RSD:

Response Surface Design

ANOVA:

Analysis of variance

LOD:

Limit of detection

LOQ:

Limit of quantification

ICH:

International Council for Harmonization

DPs:

Degradation products

CQAs:

Critical quality attributes

CAAs:

Critical analytical attributes

AMGS:

Analytical method greenness score

CMAs:

Critical material attributes

AGREE:

Appraisal of Guidelines, Research and Evaluation

GAC:

Green analytical chemistry

GAPI:

Green analytical process index

References

  1. Zigart N, Casa Z (2020) Development of a stability-indicating analytical method for determination of venetoclax using AQbD principles. ACS Omega 5:17726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. International council for Harmonization (2003) ICH Topic Q 1 A (R2) Stability Testing of new Drug Substances and Products Step 5 Note for guidance on stability testing: stability testing of new drug substances and products

  3. Sehrawat R, Maithani M, Singh R (2010) Regulatory aspects in development of stability-indicating methods: a review. Chromatographia 72:1–6. https://doi.org/10.1365/S10337-010-1612-Z

    Article  CAS  Google Scholar 

  4. Kalal DJ, Redasani VK (2022) Stability-indicating RP-HPLC method development and validation for estimation of Mupirocin calcium in bulk and in pharmaceutical formulation. Futur J Pharm Sci. https://doi.org/10.1186/S43094-022-00412-W

    Article  Google Scholar 

  5. Bhavna BS, Ojha A (2022) International Council for Harmonisation (ICH) guidelines. Regulatory Affairs in the Pharmaceutical Industry. Elsevier, Amsterdam, pp 47–74

    Chapter  Google Scholar 

  6. Cui Y, Li Y, Fan L et al (2021) UPLC-MS/MS method for the determination of Lenvatinib in rat plasma and its application to drug-drug interaction studies. J Pharm Biomed Anal 206:114360. https://doi.org/10.1016/J.JPBA.2021.114360

    Article  CAS  PubMed  Google Scholar 

  7. Tahara M, Kiyota N, Yamazaki T et al (2017) Lenvatinib for anaplastic thyroid cancer. Front Oncol. https://doi.org/10.3389/fonc.2017.00025

    Article  PubMed  PubMed Central  Google Scholar 

  8. Chellapan S, Datta D, Kumar S, Uslu H (2022) Statistical modeling and optimization of itaconic acid reactive extraction using response surface methodology (RSM) and artificial neural network (ANN). Chem Data Collect 37:47–55. https://doi.org/10.1016/j.cdc.2021.100806

    Article  CAS  Google Scholar 

  9. Al-Salama ZT, Syed YY, Scott LJ (2019) Lenvatinib: a review in hepatocellular carcinoma. Drugs 79:665–674. https://doi.org/10.1007/S40265-019-01116-X

    Article  CAS  PubMed  Google Scholar 

  10. Blessy M, Patel RD, Prajapati PN, Agrawal YK (2014) Development of forced degradation and stability indicating studies of drugs—a review. J Pharm Anal 4:159–165. https://doi.org/10.1016/j.jpha.2013.09.003

    Article  CAS  PubMed  Google Scholar 

  11. Motzer RJ, Taylor MH, Evans TRJ et al (2022) Lenvatinib dose, efficacy, and safety in the treatment of multiple malignancies. Expert Rev Anticancer Ther 22:383–400. https://doi.org/10.1080/14737140.2022.2039123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Peterson JJ, Lief K (2009) The ICH Q8 definition of design space: a comparison of the overlapping means and the Bayesian predictive approaches. AIChE Annu Meet Conf Proc. https://doi.org/10.1198/SBR.2009.08065

    Article  Google Scholar 

  13. Park G, Kim MK, Go SH et al (2022) Analytical quality by design (AQbD) approach to the development of analytical procedures for medicinal plants. Plants 11:2960

    Article  PubMed  PubMed Central  Google Scholar 

  14. Del Vecchio RJ (2007) Design of experiments. Handbook of vinyl formulating, 2nd edn. Elsevier, Amsterdam, pp 515–527

    Google Scholar 

  15. Muchakayala SK, Katari NK, Saripella KK et al (2022) 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 1679:463380. https://doi.org/10.1016/j.chroma.2022.463380

    Article  CAS  PubMed  Google Scholar 

  16. Beydoun A, Dupont S, Zhou D et al (2020) Current role of carbamazepine and oxcarbazepine in the management of epilepsy. Seizure Eur J Epilepsy 83:251–263. https://doi.org/10.1016/j.seizure.2020.10.018

    Article  Google Scholar 

  17. Sajid M, Talanta JP-W (2022) Green analytical chemistry metrics: a review. Talanta. https://doi.org/10.1016/j.talanta.2021.123046

    Article  PubMed  Google Scholar 

  18. Lopez-Lorente A, Chemistry FP-P (2022) The ten principles of green sample preparation. TrAC Trends Anal Chem 148:116530

    Article  CAS  Google Scholar 

  19. Becker J, Manske C, Chemistry SRG and S (2022) Undefined Green chemistry and sustainability metrics in the pharmaceutical manufacturing sector. Elsevier, Amsterdam

    Google Scholar 

  20. Dhage SD, Shisodiya KK (2013) Application of green chemistry in susstainable development. Int Res J Pharm 4:1–4. https://doi.org/10.7897/2230-8407.04701

    Article  CAS  Google Scholar 

  21. El-Sayed HM, Abdellatef HE, Hendawy HAM et al (2023) DoE-enhanced development and validation of eco-friendly RP-HPLC method for analysis of safinamide and its precursor impurity: QbD approach. Microchem J 190:108730. https://doi.org/10.1016/j.microc.2023.108730

    Article  CAS  Google Scholar 

  22. Muchakayala SK, Katari NK, Saripella KK et al (2022) AQbD based green UPLC method to determine mycophenolate mofetil impurities and Identification of degradation products by QToF LCMS. Sci Rep 121(12):1–18. https://doi.org/10.1038/s41598-022-22998-0

    Article  CAS  Google Scholar 

  23. Soliman SS, Sedik GA, Elghobashy MR et al (2022) Greenness assessment profile of a QbD screen-printed sensor for real-time monitoring of sodium valproate. Microchem J 182:107859. https://doi.org/10.1016/j.microc.2022.107859

    Article  CAS  Google Scholar 

  24. Mohamed D, Fouad MM (2020) Application of NEMI, analytical eco-scale and GAPI tools for greenness assessment of three developed chromatographic methods for quantification of sulfadiazine and trimethoprim in bovine meat and chicken muscles: comparison to greenness profile of reporte. Microchem J. https://doi.org/10.1016/j.microc.2020.104873

    Article  Google Scholar 

  25. Sheldon R, Bode M, Chemistry SAG, S, 2022 U (2022) Metrics of green chemistry: waste minimization. Curr Opin Green Sustain Chem. https://doi.org/10.1016/j.cogsc.2021.100569

    Article  Google Scholar 

  26. Ferreira S, Brito T, Santana A et al (2022) Greenness of procedures using NADES in the preparation of vegetal samples: comparison of five green metrics. Talanta Open 6:100131

    Article  Google Scholar 

  27. Bandla J, Ganapaty S (2018) New stability-indicating ultra performance liquid chromatography method development and validation of lenvatinib mesylate in bulk drug and pharmaceutical dosage forms. Asian J Pharm Clin Res 11:140–143. https://doi.org/10.22159/ajpcr.2018.v11i9.26766

    Article  CAS  Google Scholar 

  28. Bang PP, Bhatt HG (2023) Development of green RP- and green NP-HPTLC methods for estimation of lenvatinib and comparative evaluation by AGREE. ACS Sustain Chem Eng 11:2249–2263. https://doi.org/10.1021/ACSSUSCHEMENG.2C05767

    Article  CAS  Google Scholar 

  29. Sultana M, Res DR (2020) Stability indicating method development and validation for simultaneous estimation of dasatinib and lenvatinib by using uplc in pharmaceutical dosage form. World J Pharm 9:1548–1560. https://doi.org/10.20959/wjpr202014-18875

    Article  CAS  Google Scholar 

  30. Patel M, Kothari C (2020) Comprehensive stability-indicating method development of Avanafil Phosphodiesterase type 5 inhibitor using advanced quality-by-design approach. J Anal Sci Technol 11:29. https://doi.org/10.1186/s40543-020-00228-4

    Article  CAS  Google Scholar 

  31. Gundecha S, Patel M, Mayur YC (2022) An application of quality by design and analytical greenness assessment approach for the development of erlotinib stability indicating method. Chromatographia 85:575–588. https://doi.org/10.1007/S10337-022-04167-7

    Article  CAS  Google Scholar 

  32. Raposo F, Ibelli-Bianco C (2020) Performance parameters for analytical method validation: controversies and discrepancies among numerous guidelines. TrAC Trends Anal Chem 129:115913

    Article  CAS  Google Scholar 

  33. Mishra V, Thakur S, Patil A, Shukla A (2018) Quality by design (QbD) approaches in current pharmaceutical set-up. Expert Opin Drug Deliv 15:737–758. https://doi.org/10.1080/17425247.2018.1504768

    Article  CAS  PubMed  Google Scholar 

  34. Patel KY, Dedania ZR, Dedania RR, Patel U (2021) QbD approach to HPLC method development and validation of ceftriaxone sodium. Futur J Pharm Sci. https://doi.org/10.1186/S43094-021-00286-4

    Article  Google Scholar 

  35. Zagalo DM, Silva BMA, Silva C et al (2022) A quality by design (QbD) approach in pharmaceutical development of lipid-based nanosystems: a systematic review. J Drug Deliv Sci Technol. https://doi.org/10.1016/j.jddst.2022.103207

    Article  Google Scholar 

  36. Palandurkar K, Bhandre R, Boddu SHS et al (2023) Quality risk assessment and DoE—practiced validated stability-indicating chromatographic method for quantification of Rivaroxaban in bulk and tablet dosage form. Acta Chromatogr 35:10–20. https://doi.org/10.1556/1326.2021.00978

    Article  CAS  Google Scholar 

  37. Raska CS, Bennett TS, Goodberlet SA (2010) Risk-based analytical method transfer: application to large multi-product transfers. Anal Chem 82:5932–5936. https://doi.org/10.1021/ac1008892

    Article  CAS  PubMed  Google Scholar 

  38. Deidda R, Orlandini S, Hubert P, Hubert C (2018) Risk-based approach for method development in pharmaceutical quality control context: a critical review. J Pharm Biomed Anal 161:110–121. https://doi.org/10.1016/j.jpba.2018.07.050

    Article  CAS  PubMed  Google Scholar 

  39. Chaudhari SR, Shirkhedkar AA (2020) Application of Plackett-Burman and central composite designs for screening and optimization of factor influencing the chromatographic conditions of HPTLC method for quantification of efonidipine hydrochloride. J Anal Sci Technol. https://doi.org/10.1186/S40543-020-00246-2

    Article  Google Scholar 

  40. Valmorida JS, Castillo-Israel KAT (2018) Application of Plackett-Burman experimental design in the development of muffin using adlay flour. IOP Conf Ser Earth Environ Sci. https://doi.org/10.1088/1755-1315/102/1/012081

    Article  Google Scholar 

  41. Januardi WE (2020) A review of response surface methodology approach in supply chain management. ACM Int Conf Proc Ser. https://doi.org/10.1145/3400934.3400993

    Article  Google Scholar 

  42. Myers RH, Montgomery DC, Geoffrey Vining G et al (2004) Response surface methodology: a retrospective and literature survey. J Qual Technol 36:53–78

    Article  Google Scholar 

  43. de Oliveira LG, de Paiva AP, Balestrassi PP et al (2019) Response surface methodology for advanced manufacturing technology optimization: theoretical fundamentals, practical guidelines, and survey literature review. Int J Adv Manuf Technol 104:1785–1837. https://doi.org/10.1007/S00170-019-03809-9

    Article  Google Scholar 

  44. Mark H (2003) Application of an improved procedure for testing the linearity of analytical methods to pharmaceutical analysis. J Pharm Biomed Anal 33:7–20. https://doi.org/10.1016/S0731-7085(03)00346-7

    Article  CAS  PubMed  Google Scholar 

  45. Mollica JA, Ahuja S, Cohen J (1978) Stability of pharmaceuticals. J Pharm Sci 67:443–465. https://doi.org/10.1002/jps.2600670405

    Article  CAS  PubMed  Google Scholar 

  46. Moema D, Makwakwa T, BG-J of F (2023) undefined by high pressure liquid chromatography: Greenness assessment using national environmental methods index label (NEMI), green analytical procedure index (GAPI). Elsevier, Amsterdam

    Google Scholar 

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  1. Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKMs NMIMS, V. L. Mehta Road, Vile Parle (W), Mumbai, Maharashtra, 400056, India

    Payal Tiwari & Mital Patel

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Tiwari, P., Patel, M. Advancing Quality and Environmental Responsibility: A Stability-Indicating LC Method Development for Lenvatinib Through QbD and Green Chemistry. Chromatographia 86, 579–593 (2023). https://doi.org/10.1007/s10337-023-04271-2

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