BIOANALYTICAL METHOD FOR THE ESTIMATION OF ZIFTOMENIB AND ITS APPLICATION TO PHARMACOKINETIC STUDIES USING LC-MS/MS
DOI:
https://doi.org/10.22159/ajpcr.2026v19i3.57922Keywords:
Liquid chromatography-tandem mass spectrometry,, Ziftomenib, USFDA guidelines, Validation, Rat plasmaAbstract
Objectives: Food and Drug Administration (FDA) approved and menin inhibitor category drug of ziftomenib was used in the treatment of acute myeloid leukemia. For the bioanalytical approach of ziftomenib, a quick and easy, exact, active, and repeatable liquid chromatography-tandem mass spectrometry methodology was created, employing revumenib as an internal standard.
Methods: In this study, a symmetry C18 column (150 mm × 4.6 mm, 3.5 μm) was used for separation. Buffer (1 ml per chloric acid in 1 lt of water) and acetonitrile (60:40% v/v) as the mobile phase combination with 1 mL/min flow rate at room temperature.
Results: The calibration curve was linear in the range of 5–200 ng/mL of ziftomenib with r2 = 0.9997. Matrix effect, accuracy, and precision results were within the acceptable limits according to the United States FDA (USFDA) requirements, we found that the drugs were stable throughout the stability trials. The validated method had effectively performed the drug’s pharmacokinetic investigations.
Conclusion: The application denotes that all the parameters of system suitability, specificity, linearity, and accuracy are in good agreement with USFDA guidelines and applied effectively for the investigation of pharmacokinetic studies in rats.
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References
1. Taléns-Visconti R, Díez-Sales O, De Julián-Ortiz JV, Nácher A. Nanoliposomes in cancer therapy: Marketed products and current clinical trials. Int J Mol Sci. 2022;23(8):4249. doi: 10.3390/ ijms23084249, PMID 35457065
2. Kwakman JJ, Elshot YS, Punt CJ, Koopman M. Management of cytotoxic chemotherapy-induced hand-foot syndrome. Oncol Rev. 2020;14(1):442. doi: 10.4081/oncol.2020.442, PMID 32431787
3. Kantarjian HM, Dinardo CD, Kadia TM, Daver NG, Altman JK, Stein EM, et al. Acute myeloid leukemia management and research in 2025. CA Cancer J Clin. 2025;75(1):46-67. doi: 10.3322/caac.21873, PMID 39656142
4. Goulart H, Kantarjian H, Pemmaraju N, Daver N, Dinardo CD, Rausch CR, et al. Venetoclax-based combination regimens in acute myeloid leukemia. Blood Cancer Discov. 2025;6(1):23-37. doi: 10.1158/2643-3230.bcd-24-0171, PMID 39565177
5. Senapati P, Bhattacharya A, Das S, Dey S, Sudarshan D, Shyla G, et al. Histone chaperone nucleophosmin regulates transcription of key genes involved in oral tumorigenesis. Mol Cell Biol. 2022;42(2):e0066920. doi: 10.1128/mcb.00669-20, PMID 34898280
6. Loberg MA, Bell RK, Goodwin LO, Eudy E, Miles LA, SanMiguel JM, et al. Sequentially inducible mouse models reveal that Npm1 mutation causes malignant transformation of Dnmt3a-mutant clonal hematopoiesis. Leukemia. 2019;33(7):1635-49. doi: 10.1038/ s41375-018-0368-6, PMID 30692594
7. Jyotsna VP, Malik E, Birla S, Sharma A. Novel MEN 1 gene findings in rare sporadic insulinoma--a case control study. BMC Endocr Disord. 2015;15:44. doi: 10.1186/s12902-015-0041-2, PMID 26307114
8. Andersson AK, Ma J, Wang J, Chen X, Gedman AL, Dang J, et al. The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias. Nat Genet. 2015;47(4):330-7. doi: 10.1038/ ng.3230, PMID 25730765
9. Rausch J, Dzama MM, Dolgikh N, Stiller HL, Bohl SR, Lahrmann C, et al. Menin inhibitor ziftomenib (KO-539) synergizes with drugs targeting chromatin regulation or apoptosis and sensitizes acute myeloid leukemia with MLL rearrangement or NPM1 mutation to venetoclax. Haematologica. 2023;108(10):2837-43. doi: 10.3324/haematol.2022.282160, PMID 37102614
10. Paul K, Jaswanth Gowda BH, Chandan RS. Development and validation of a novel RP-HPLC method for determination of Remdesivir: Investigation of the greenness for the proposed method. Results Chem. 2025;16:102382. doi: 10.1016/j.rechem.2025.102382.
11. Shareef SN, Padmavathi KV, Aravind S, Subbarao M. Bio analytical method for simultaneous estimation of capecitabine and docetaxel and its application to pharmacokinetic studies using LC-MS/MS. Int J App Pharm. 2024;16(4):275-82. doi: 10.22159/ ijap.2024v16i4.50125.
12. Rayinuthala Y, Medepalli DR, Lakshmanarao A. Bio-analytical method development and validation of finasteride, tadalafil, and its application to pharmacokinetic studies in rat plasma by using LC-MS/MS. Int J App Pharm. 2024;16(5):300-8. doi: 10.22159/ijap.2024v16i5.50858
13. Srinivasulu D, Sastry BS, Omprakash G. Development and validation of new RP-HPLC method for determination of pioglitazone hcl in pharmaceutical dosage forms. Int J Chem Res. 2010;1(1):18-20.
14. Pimpale A, Kakde R. Stability-indicating method development and validation for the estimation of rosuvastatin calcium in pharmaceutical dosage form by reverse phase-high performance liquid chromatography. Int J Chem Res. 2020;4(4):9-16.
15. Rathore MK, Reddy TR. Tandem mass spectrometric method for the trace level determination of 2-aminopyridine: A potential genotoxic impurity in tenoxicam API. Int J Pharm Pharm Sci. 2024;16(4):50-6.
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