Development and validation of an HPLC method for simultaneous determination of imatinib mesylate and rifampicin

Göknil Coşkun; Gülen Melike Demirbolat

Development and validation of an HPLC method for simultaneous determination of imatinib mesylate and rifampicin

Abstract

Imatinib mesylate is used to treat various cancerous diseases. Lately, investigations have focused on the enhancement of chemotherapeutic agents. Thus, rifampicin is a promising candidate due to its chemosensitizing potential beyond its anti-infectious effects. In this study, a reliable separation method for imatinib mesylate and rifampicin have been developed. The HPLC analysis were performed on a C18 column (150 x 4.6 mm, 3 μm particle size) at 25 °C. The best UV decetection was observed at 254 nm. The mobile phase was set as acetonitrile and TEA/phosphate buffer (pH: 7.04; 0.1 M) (50:50, v/v) with isocratic elution. The flow rate was set as 0.8 mL/min. The method validation was performed according to the international guidelines with respect to selectivity, linearity, precision and accuracy, recovery and sensitivity. The detection and quantification limit of the method were 0.63 μg/mL and 1.90 μg/mL, respectively for imatinib mesylate, and 3.04 μg/mL and 9.22 μg/mL for rifampicin. The method was linear in the range of 10–90 μg/mL with determination coefficients (r2≥0.99) for both drugs. Precision, accuracy and recovery values (RSD<3%) of the method was convincing. Considering the various usage of imatinib mesylate and rifampicin, the developed method is applicable to different dosage forms.

Keywords

References

[1] Bingöl-Özakpınar Ö, Türe A, Küçükgüzel İ. Molecular modeling and assessment of cytotoxic and apoptotic potential of imatinib analogues featuring (thio)urea motifs in human leukemia and lymphoma. J Res Pharm. 2020; 24(6): 801-811. [CrossRef]
[2] Türe A, Kahraman DC, Cetin-Atalay R, Helvacıoğlu S, Charehsaz M, Küçükgüzel I. Synthesis, anticancer activity, toxicity evaluation and molecular docking studies of novel phenylaminopyrimidine—(thio)urea hybrids as potential kinase inhibitors. Comput Biol Chem. 2019, 78: 227-241. [CrossRef]
[3] Zwolak P, Jasinski P, Terai K, Gallus NJ, Ericson ME, Clohisy DE, Dudek, AZ. Addition of receptor tyrosine kinase inhibitor to radiation increases tumor control in an orthotopic murine model of breast cancer metastasis in bone. Eur J Cancer. 2008; 44(16): 2506–2517. [CrossRef]
[4] Blume-Jensen P, Hunter T. Oncogenic kinase signaling. Nature. 2001; 411: 355-365. [CrossRef]
[5] Demirbolat GM, Altintas L, Yilmaz Ş, Degim IT. Development of Orally Applicable, Combinatorial Drug-Loaded Nanoparticles for the Treatment of Fibrosarcoma. J Pharm Sci. 2018; 107(5): 1398-1407. [CrossRef]
[6] Mansour HH, El Kiki SM, Ibrahim AB, Omran MM. Effect of L-carnitine on cardiotoxicity and apoptosis induced by imatinib through PDGF/ PPARγ /MAPK pathways. Arch. Biochem. 2021; 704:108866. [CrossRef]
[7] D’Avolioa A, Simielea M, Francia SD, Ariaudo A, Baiettoa L. Cusato J, Fava C, Saglio G, Di Carlo F, Di Perri G. HPLC–MS method for the simultaneous quantification of the antileukemia drugs imatinib, dasatinib and nilotinib in human peripheral blood mononuclear cell (PBMC). J Pharm Biomed Anal. 2012; 59: 109–116. [CrossRef]
[8] Francia SD, D’Avolio A, Martinoa FD, Pirroa E, Baietto L, Siccardi M, Simiele M, Racca S, Saglio G, Di Carlo F, Di Perri G. New HPLC–MS method for the simultaneous quantification of the antileukemia drugs imatinib, dasatinib, and nilotinib in human plasma. J Chromatogr B. 2009; 877: 1721–1726. [CrossRef]

[9] Asadpour-Zeynali K, Elhameh S. Simultaneous Spectrophotometric Determination of Rifampicin, Isoniazid and Pyrazinamide in a Single Step. Iran J Pharm Res. 2016; 15: 713-723.
[10] Zhu JH, Wang BW, Pan M, Zeng YN, Rego H, Javid B. Rifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes in rpoB transcription. Nat Commun. 2018; 9(1):4218. [CrossRef]
[11] Yulug B, Hanoglu L, Ozansoy M, Isik D, Kilic U, Kilic E, Schabitz WR. Therapeutic role of rifampicin in Alzheimer's disease. Psychiatry Clin Neurosci. 2018; 72(3):152-9. [CrossRef]
[12] Chikaraishi Y, Matsunaga N, Shimazawa M, Hara H. Rifampicin inhibits the retinal neovascularization in vitro and in vivo. Exp Eye Res. 2008; 86(1):131-7. [CrossRef]
[13] Kilic U, Kilic E, Lingor P, Yulug B, Bahr M. Rifampicin inhibits neurodegeneration in the optic nerve transection model in vivo and after 1-methyl-4-phenylpyridinium intoxication in vitro. Acta Neuropathol. 2004; 108(1):65-8. [CrossRef]
[14] Chakraborty A, Panda AK, Ghosh R, Roy I, Biswas A. Depicting the DNA binding and photo-nuclease ability of anti-mycobacterial drug rifampicin: A biophysical and molecular docking perspective. Int J Biol Macromol. 2019; 127:187-96. [CrossRef]
[15] Shumyantseva VV, Bulko TV, Tikhonova EG, Sanzhakov MA, Kuzikov AV, Masamrekh RA, Pergushov DV, Schacher FH, Sigolaeva LV. Electrochemical studies of the interaction of rifampicin and nanosome/rifampicin with dsDNA. Bioelectrochemistry. 2021; 140:107736. [CrossRef]
[16] Fardel O, Lecureur V, Loyer P, Guillouzo A. Rifampicin Enhances Anticancer Drug Accumulation and Activity in Multidrug-Resistant Cells. Biochem Pharmacol. 1995; 49(9):1255-60. [CrossRef]
[17] Bukowski K, Kciuk M, Kontek R. Mechanisms of Multidrug Resistance in Cancer Chemotherapy. Int J Mol Sci. 2020; 21(9):3233. [CrossRef]
[18] Kim JH, Nam WS, Kim SJ, Kwon OK, Seung EJ, Jo JJ, Shresha R, Lee TH, Jeon TW, Ki SH, Lee HS, Lee S. Mechanism Investigation of Rifampicin-Induced Liver Injury Using Comparative Toxicoproteomics in Mice. Int J Mol Sci. 2017; 18(7):1417. [CrossRef]
[19] Shichiri M, Fukai N, Kono Y, Tanaka Y. Rifampicin as an oral angiogenesis inhibitor targeting hepatic cancers. Cancer Res. 2009; 69(11):4760-8. [CrossRef]
[20] Shichiri M, Tanaka Y. Inhibition of cancer progression by rifampicin: involvement of antiangiogenic and anti-tumor effects. Cell Cycle. 2010; 9(1):64-8. [CrossRef]
[21] Hashimoto S, Honda K, Fujita K, Miyachi Y, Isoda K, Misaka K, Suga Y, Kato S, Tsuchia H, Kato Y, Okajima M, Taniguchi T, Shimada T, Sai Y. Effect of coadministration of rifampicin on the pharmacokinetics of linezolid: clinical and animal studies. J Pharm Health Care Sci. 2018; 4:27. [CrossRef]
[22] Saad EA, Kiwan HA, Hassanien MM, Al-Adl HE. Synthesis, characterization, and antitumor activity of a new iron-rifampicin complex: A novel prospective antitumor drug. J Drug Deliv Sci Technol. 2020; 57:101671. [CrossRef] [23] Wohlfart J, Scherf-Clave, O, Kinzig M, Sörgel F, Holzgrabe U. The nitrosamine contamination of drugs, part 3: Quantification of 4-Methyl-1-nitrosopiperazine in rifampicin capsules by LC-MS/HRMS. J Pharm Biomed Anal. 2021; 203:114205. [CrossRef]
[24] Wasik A, McCourt J, Buchgraber M. Simultaneous determination of nine intense sweeteners in foodstuffs by high performance liquid chromatography and evaporative light scattering detection--development and single-laboratory validation. J Chromatogr A. 2007; 1157(1-2):187-96. [CrossRef]
[25] De Meulder M, Remmerie BMM, De Vries R. Sips LLA, Boom S, Hooijschuur EWJ, Merbel NC, Timmerman PMMBL. Validated LC-MS/MS methods for the determination of risperidone and the enantiomers of 9-hydroxyrisperidone in human plasma and urine. J Chromatogr B. 2008; 870(1):8-16. [CrossRef]
[26] Shukla RS, Pandey S, Bargale R, Pateland A, Tiwari M. Novel HPLC analysis of cefadroxil in bulk formulation. Asian J Pharm. 2008; 2(2):106-9. [CrossRef]
[27] Sutradhar I, Zaman MH. Evaluation of the effect of temperature on the stability and antimicrobial activity of rifampicin quinone. J Pharm Biomed Anal. 2021; 197:113941. [CrossRef]
[28] Goutal S, Auvity S, Legrand T, Hauquier F, Cisternino S, Chapy H, Saba W, Tournier N. Validation of a simple HPLC-UV method for rifampicin determination in plasma: Application to the study of rifampicin arteriovenous concentration gradient. J Pharm Biomed Anal. 2016; 10(123):173-8. [CrossRef]
[29] Khadka P, Sinha S, Tucker IG, Dummer J, Hill PC, Katare R, Das S.C. Pharmacokinetics of rifampicin after repeated intra-tracheal administration of amorphous and crystalline powder formulations to Sprague Dawley rats. Eur J Pharm Biopharm. 2021; 162:1-11. [CrossRef]
[30] Roth O, Spreux-Varoquaux O, Bouchet S, Rousselot P, Castaigne S, Rigaudeau S, Raggueneau V, Therond P, Devillier P, Molimard M, Maneglier B. Imatinib assay by HPLC with photodiode-array UV detection in plasma from patients with chronic myeloid leukemia: Comparison with LC-MS/MS. Clin Chim Acta. 2010; 411(3-4):140-6. [CrossRef]
[31] Golabchifar AA, Rouini MR, Shafaghi B, Rezaee S, Foroumadi A, Khoshayand, MR. Optimization of the simultaneous determination of imatinib and its major metabolite, CGP74588, in human plasma by a rapid HPLC method using D-optimal experimental design. Talanta. 2011; 85(5):2320-9. [CrossRef]
[32] De Francia S, D'Avolio A, De Martino F, Pirro E, Baietto L, Siccardi, M. Simiele M, Racca S, Saglio G, Di Carlo F, Di Perri G. New HPLC-MS method for the simultaneous quantification of the antileukemia drugs imatinib, dasatinib, and nilotinib in human plasma. J Chromatogr B. 2009; 877(18-19):1721-6. [CrossRef]
[33] Moldoveanu SC, David V. Essentials in Modern HPLC Separations. Chapter 2 - Parameters that Characterize HPLC Analysis. Elsevier Publications, Holland, 2013, pp.53-83. [CrossRef]

Details

Primary Language

English

Subjects

Pharmaceutical Chemistry, Pharmaceutical Delivery Technologies

Journal Section

Research Article

Authors

Göknil Coşkun ^*
0000-0001-5168-3866
Türkiye

Gülen Melike Demirbolat
0000-0001-5621-5818
Türkiye

Publication Date

June 28, 2025

Submission Date

May 30, 2022

Acceptance Date

June 21, 2022

Published in Issue

Year 2022 Volume: 26 Number: 5

IZ

https://izlik.org/JA48KL55WF

Cite

RIS / Bibtex

APA

Coşkun, G., & Demirbolat, G. M. (2025). Development and validation of an HPLC method for simultaneous determination of imatinib mesylate and rifampicin. Journal of Research in Pharmacy, 26(5), 1443-1452. https://izlik.org/JA48KL55WF

AMA

1.Coşkun G, Demirbolat GM. Development and validation of an HPLC method for simultaneous determination of imatinib mesylate and rifampicin. J. Res. Pharm. 2025;26(5):1443-1452. https://izlik.org/JA48KL55WF

Chicago

Coşkun, Göknil, and Gülen Melike Demirbolat. 2025. “Development and Validation of an HPLC Method for Simultaneous Determination of Imatinib Mesylate and Rifampicin”. Journal of Research in Pharmacy 26 (5): 1443-52. https://izlik.org/JA48KL55WF.

EndNote

Coşkun G, Demirbolat GM (June 1, 2025) Development and validation of an HPLC method for simultaneous determination of imatinib mesylate and rifampicin. Journal of Research in Pharmacy 26 5 1443–1452.

IEEE

[1]G. Coşkun and G. M. Demirbolat, “Development and validation of an HPLC method for simultaneous determination of imatinib mesylate and rifampicin”, J. Res. Pharm., vol. 26, no. 5, pp. 1443–1452, June 2025, [Online]. Available: https://izlik.org/JA48KL55WF

ISNAD

Coşkun, Göknil - Demirbolat, Gülen Melike. “Development and Validation of an HPLC Method for Simultaneous Determination of Imatinib Mesylate and Rifampicin”. Journal of Research in Pharmacy 26/5 (June 1, 2025): 1443-1452. https://izlik.org/JA48KL55WF.

JAMA

1.Coşkun G, Demirbolat GM. Development and validation of an HPLC method for simultaneous determination of imatinib mesylate and rifampicin. J. Res. Pharm. 2025;26:1443–1452.

MLA

Coşkun, Göknil, and Gülen Melike Demirbolat. “Development and Validation of an HPLC Method for Simultaneous Determination of Imatinib Mesylate and Rifampicin”. Journal of Research in Pharmacy, vol. 26, no. 5, June 2025, pp. 1443-52, https://izlik.org/JA48KL55WF.

Vancouver

1.Göknil Coşkun, Gülen Melike Demirbolat. Development and validation of an HPLC method for simultaneous determination of imatinib mesylate and rifampicin. J. Res. Pharm. [Internet]. 2025 Jun. 1;26(5):1443-52. Available from: https://izlik.org/JA48KL55WF