Skip to content
2000
image of Fluorescence Microwell and Flow Injection Platforms for Determination of Brexpiprazine

Abstract

Introduction

Brexpiprazole (BXP) is a novel dopamine and serotonin partial agonist used for the treatment of schizophrenia. It has recently gained approval for the treatment of agitation associated with dementia due to Alzheimer’s disease. This study aimed to enhance the fluorescence intensity of BXP by turning “OFF” its photoinduced electron transfer and employing the enhanced fluorescence in establishing two analytical platforms for the direct quantification of BXP in commercial pharmaceutical tablets and plasma.

Methods

Two analytical methods were developed: a microwell spectrofluorimetric assay combined with a fluorescence microplate reader (MW-SFA) and flow injection analysis coupled with a fluorescence detector (FIA-FD). Both platforms underwent optimization and validation.

Results

The linear ranges of the platforms were 5–500 for MW-SFA and 20–2000 ng/mL for FIA-FD. The limits of quantification were 12.9 and 25.5 ng/mL for MW-SFA and FIA-FD, respectively. Both platforms showed high precision and accuracy, with relative standard deviation (RSD) values ranging from 1.2% to 1.9% and recovery values ranging from of 98.5% to 102.4%. The proposed platforms were successfully applied to the analysis of BXP in tablets, and the recovery values ranged from 99.2% to 101.4% with RSD values ranged from 1.1% to 1.8%. The suggested platforms were also employed for analyzing plasma samples containing BXP, achieving an accuracy of at least 98.6%. The greenness levels of both platforms were confirmed using three metric tools.

Discussion

The enhancement of native fluorescence of BXP resulted in high sensitivity of both MW-SFA and FIA-FD platforms. The employment of microwell and flow injection approaches enhanced the accuracy and precision of both platforms. Additionally, both platforms offered a high-throughput, cost-effective, and green analytical approach.

Conclusion

The proposed platforms feature simple procedures, high sensitivity, high throughput, and environmental greenness. The platforms are highly recommended as effective tools for BXP determination in pharmaceutical quality control and clinical laboratories.

Loading

Article metrics loading...

/content/journals/cac/10.2174/0115734110369606250710043835
2025-10-27
2025-10-29
Loading full text...

Full text loading...

References

  1. FDA approves Otsuka and Lundbeck’s Rexulti (brexpiprazole) as adjunctive treatment for adults with major depressive disorder and as a treatment for adults with schizophrenia. 2015 Available from: www.otsuka-us.com/newsroom/Pages/NewsArticle.aspx?ItemId=13
  2. FDA approves first drug to treat agitation symptoms associated with dementia due to Alzheimer’s disease. 2025 Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-agitation-symptoms-associated-dementia-due-alzheimers-disease#:~:text=Today%2C%20the%20U.S.%20Food%20and,treatment%20option%20for%20this%20indication
  3. Siwek M. Wojtasik-Bakalarz K. Krupa A.J. Chrobak A.A. Brexpiprazole-pharmacologic properties and use in schizophrenia and mood disorders. Brain Sci. 2023 13 3 397 10.3390/brainsci13030397 36979208
    [Google Scholar]
  4. Salama F.M. Attia K.A. Said R.A. El-Olemy A. Abdel-raoof A.M. RP-HPLC method for determination of brexpiprazole in the presence of its oxidative induced degradation product. Asian J. Pharm. Health Sci. 2018 8 1886 1893
    [Google Scholar]
  5. Pulusu V.S. Routhu K. Chikkaswamy S. Quantitative determination of brexpiprazole by RP-HPLC method. Pharm. Anal. Acta 2019 10 610 10.35248/2153‑2435.19.10.610
    [Google Scholar]
  6. Bhaybhang M. Jadhav P. RP-HPLC method development and validation for estimation of brexpiprazole in bulk drug and dosage form. World J. Pharm. Res. 2020 9 15 1473 1491 10.20959/wjpr202015‑19380
    [Google Scholar]
  7. Zou Q. Yan R. Liu W. Wei P. A validated quantification method for brexpiprazole in dog plasma. J. Chromatogr. Sci. 2018 56 8 702 708 10.1093/chromsci/bmy045
    [Google Scholar]
  8. Jagdale A.S. Pendbhaje N.S. Nirmal R.V. Bachhav P.M. Sumbre D.B. Development and validation of RP-HPLC method for estimation of brexpiprazole in its bulk and tablet dosage form using quality by design approach. Future J. Pharm. Sci. 2021 7 1 12 10.1186/s43094‑021‑00293‑5
    [Google Scholar]
  9. Nadella P.N. Nadh Ratnakaram V. Navuluri S. QbD-based UPLC method for quantification of brexpiprazole in presence of impurities and application to in vitro dissolution. J. Chromatogr. Sci. 2021 59 3 223 240 10.1093/chromsci/bmaa099 33333554
    [Google Scholar]
  10. Zhang Y. Wang C. Xu X. Zhao Z. Su X. Zhu H. Determination and metabolism of brexpiprazole following baicalin to rats by a novel developed UPLC-MS/MS. Arab. J. Chem. 2021 14 12 103430 10.1016/j.arabjc.2021.103430
    [Google Scholar]
  11. Thakkar A.M. Chhalotiya U.K. Parekh N. Desai J.V. Shah D.A. Stability indicating TLC method for quantification of brexpiprazole in bulk and its pharmaceutical dosage form and determination of content uniformity. J. Chromatogr. Sci. 2019 57 7 644 652 10.1093/chromsci/bmz039 31095672
    [Google Scholar]
  12. Vahora S. Chhalotiya U.K. Kachhiya H. Tandel J. Shah D. Simultaneous quantification of brexpiprazole and sertraline HCl in synthetic mixture by thin-layer chromatography method. J. Planar Chromatogr. Mod. TLC 2021 34 6 549 557 10.1007/s00764‑021‑00142‑4
    [Google Scholar]
  13. Patel P. Mashru R. Novel UV spectrophotometric & chemometrics assisted 4 spectrophotometric methods for simultaneous estimation of brexpiprazole and sertraline: A statistical analysis. Pharma Innovation J. 2020 9 29 42
    [Google Scholar]
  14. Derayea S.M. Amir S Zaafan A. Nagi D.A. Oraby M. Augmentation of Brexpiprazole fluorescence through photoinduced electron transfer inhibition for the sensitive spectrofluorimetric assay of pharmaceutical dosage forms and spiked human plasma: Application to content uniformity testing. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2023 301 122948 10.1016/j.saa.2023.122948 37285746
    [Google Scholar]
  15. Thakkar A. Chhalotiya U. Parekh N. Desai J. Dalwadi H. Shah D. Quantification of brexpiprazole in bulk and its pharmaceutical dosage form by UV–visible spectroscopic and SIAM RP-HPLC method. Austin Chromatogr. 2018 5 1050 1056
    [Google Scholar]
  16. Mangotra A. Singh S.K. Volatile organic compounds: A threat to the environment and health hazards to living organisms – A review. J. Biotechnol. 2024 382 51 69 10.1016/j.jbiotec.2023.12.013 38242502
    [Google Scholar]
  17. Guo W. Chen Z. Feng Z. Li H. Zhang M. Zhang H. Cui X. Fabrication of concave microwells and their applications in micro-tissue engineering: A review. Micromachines 2022 13 9 1555 10.3390/mi13091555 36144178
    [Google Scholar]
  18. Khalil N.Y. Al Qhatani M.N. Al Qubaisi K.A. Sayed A.Y. Darwish I.A. Development of two innovative 96-microwell-based spectrophotometric assays with high throughput for determination of fluoroquinolone antibiotics in their pharmaceutical formulations. J. Appl. Spectrosc. 2022 89 1 66 74 10.1007/s10812‑022‑01327‑3
    [Google Scholar]
  19. Alzoman N.Z. Darwish I.A. Development of a green microwell spectrofluorimetric assay with high analytical throughput for the determination of selective serotonin reuptake inhibitors in pharmaceutical dosage forms and plasma. Molecules 2023 28 13 5221 10.3390/molecules28135221 37446883
    [Google Scholar]
  20. Zhao M. Wang B. Wang B. Li X. Flow injection chemiluminescence method for determination of acarbose. J. Hebei Univ. 2022 42 251 255
    [Google Scholar]
  21. Trojanowicz M. Pyszynska M. Flow-injection methods in water analysis—Recent developments. Molecules 2022 27 4 1410 10.3390/molecules27041410 35209198
    [Google Scholar]
  22. Teshima N. Murakami H. Sakai T. Development of testing methods for water quality by flow analysis. Bunseki Kagaku 2020 69 6 257 269 10.2116/bunsekikagaku.69.257
    [Google Scholar]
  23. Omarova S. Demir S. Andac M. Development of a New spectrophotometric based flow injection analysis method for the determination of copper (II). J. Taibah Univ. Sci. 2018 12 6 820 825 10.1080/16583655.2018.1521710
    [Google Scholar]
  24. Thomas I. Kavitha G. Abraham E. Fluorescence spectroscopy and its applications: A review. Int. J. Adv. Pharm. Anal. 2018 8 1 8
    [Google Scholar]
  25. Escudero D. Revising intramolecular photoinduced electron transfer (PET) from first-principles. Acc. Chem. Res. 2016 49 9 1816 1824 10.1021/acs.accounts.6b00299 27575871
    [Google Scholar]
  26. Darwish I.A. Alzoman N.Z. Dual fluorescence enhancement of loratidine by photoinduced electron transfer blocking and micellization: Application to the development of novel highly sensitive microwell spectrofluorimetric assay for analysis of dosage forms and urine samples. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2024 305 123458 10.1016/j.saa.2023.123458 37816264
    [Google Scholar]
  27. Jang Y.J. Kim B. Roh E. Kim H. Lee S.H. Micellization-induced amplified fluorescence response for highly sensitive detection of heparin in serum. Sci. Rep. 2020 10 1 9438 10.1038/s41598‑020‑66360‑8 32523015
    [Google Scholar]
  28. Karim M.R. Uddin M.S. Alam M.A. Micellar enhanced spectrofluorimetric determination of drugs: Recent advances and future prospects. J. Pharm. Anal. 2020 10 527 542
    [Google Scholar]
  29. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, ICH Harmonised Guideline, Validation of Analytical Procedure: Q2(R2). Geneva ICH 2022
    [Google Scholar]
  30. Gałuszka A. Migaszewski Z.M. Konieczka P. Namieśnik J. Analytical Eco-Scale for assessing the greenness of analytical procedures. Trends Analyt. Chem. 2012 37 61 72 10.1016/j.trac.2012.03.013
    [Google Scholar]
  31. Płotka-Wasylka J. A new tool for the evaluation of the analytical procedure: Green analytical procedure index. Talanta 2018 181 204 209 10.1016/j.talanta.2018.01.013 29426502
    [Google Scholar]
  32. Pena-Pereira F. Wojnowski W. Tobiszewski M. AGREE-analytical greenness metric approach and software. Anal. Chem. 2020 92 14 10076 10082 10.1021/acs.analchem.0c01887 32538619
    [Google Scholar]
/content/journals/cac/10.2174/0115734110369606250710043835
Loading
/content/journals/cac/10.2174/0115734110369606250710043835
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test