Generic placeholder image

Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

A Validated DBS Method for Quantitation of a Novel Mutant IDH1/2 Inhibitor, Vorasidenib Using 10 μL Mice Blood: Application to a Pharmacokinetic Study in Mice

Author(s): Sreekanth Dittakavi, Rakesh Kumar Jat and Ramesh Mullangi*

Volume 16, Issue 8, 2020

Page: [1140 - 1147] Pages: 8

DOI: 10.2174/1573412915666190802163644

Price: $65

Abstract

Background: Vorasidenib is a pan-IDH inhibitor, undergoing clinical trials for the treatment of acute myeloid leukemia.

Methods: In this paper, we present the data of method validation to quantify vorasidenib in the mice blood mice using dried blood spot (DBS) method on LC-MS/MS as per FDA bioanalytical method validation guideline. Using methanol (enriched with internal standard) as an extraction solvent followed by sonication, vorasidenib was extracted from DBS quality control samples, calibration curve samples and pharmacokinetic study samples. Baseline separation of vorasidenib and the IS in a 2.0 μL injected sample was accomplished by delivering 0.2% formic acid and acetonitrile (25:75, v/v) at a constant flowrate (1.00 mL/min) on a C18 column. The total run time was 2.0 min. Using the transition pair of m/z 415.4→260.4 for vorasidenib and m/z 583.1→186.1 for the IS, the quantitation was performed. The method linearity range was 1.00-3008.00 ng/mL.

Results: The recovery of vorasidenib ranged between 71.28%-78.14% across the tested concentrations. No matrix effect was seen. Intra- and inter-day precisions were ≤7.23% and intra- and inter-accuracies ranged between 97.1%-107%. Vorasidenib was stable for three freeze/thaw cycles, up to 7 days at room temperature and for one month at -80°C. Following intravenous and oral administration of vorasidenib to mice, it was quantifiable up to 72 h. The oral bioavailability was 51.6%.

Conclusion: All the validation parameters met the acceptance criteria as specified in the FDA regulatory guideline. The results suggest that validated DBS method can be used for pharmacokinetic studies in mice to characterize the pharmacokinetic parameters of vorasidenib post intravenous and oral administration.

Keywords: Vorasidenib, dried blood spot, LC-MS/MS, method validation, mice blood, pharmacokinetics.

Graphical Abstract

[1]
Abou Dalle, I.; DiNardo, C.D. The role of enasidenib in the treatment of mutant IDH2 acute myeloid leukemia. Ther. Adv. Hematol., 2018, 9(7), 163-173.
[http://dx.doi.org/10.1177/2040620718777467] [PMID: 30013764]
[2]
Buege, M.J.; DiPippo, A.J.; DiNardo, C.D. Evolving treatment strategies for elder leukemia 284 patients with IDH mutations. Cancers (Basel), 2018, 10(6), 187.
[http://dx.doi.org/10.3390/cancers10060187] [PMID: 29882807]
[3]
Yen, K.; Konteatis, Z.; Straley, K.; Artin, E.; David, M.; Quivoron, C.; Dang, L.; Tobin, E.; Campos, C.; Yang, H.; Nagaraja, R.; Chen, Y.; Sui, Z.; Kim, H.; Gliser, C.; Nicolay, B.; Olaharski, A.; Silverman, L.; Penard-Lacronique, V.; de Botton, S.; Biller, S.; Su, S.M.; Mellinghoff, I. Popovici-Muller1, J. AG-881, a brain penetrant, potent, pan-mutant IDH (mIDH) inhibitor for use in mIDH solid and hematologic malignancies. AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, October 26-30, 2017Philadelphia, PA
[4]
Mellinghoff, I.K.; Penas-Prado, M.; Peters, K.B.; Cloughesy, T.F.; Burris, H.A.; Maher, E.A.; Janku, F.; Cote, G.M.; Fuente, M.I.D.L.; Clarke, J.; Steelman, L.; Le, K.; Zhang, Y.; Sonderfan, A.; Hummel, D.; Schoenfeld, S.; Yen, K.; Pandya, S.S.; Wen, P.Y. Phase 1 study of AG-881, an inhibitor of mutant IDH1 and IDH2: results from the recurrent/progressive glioma populations. 23rd Annual Scientific Meeting and Education Day of the Society for Neuro-oncology (SNO), November 15-18, 2018New Orleans, LA, USA
[http://dx.doi.org/10.1093/neuonc/noy148.064]
[5]
http://investor.agios.com/news-releases/news-release-details/agios-highlights-key-2019-initiatives-broaden-potential-cancer2019.
[6]
Chernonosov, A. The use of dried blood spot for the quantitation of antihyper-tensive drug Int. J. Analy. Chem 2018.
[7]
Lim, M.D. Dried blood spots for global health diagnostics and surveillance: opportunities and challenges. Am. J. Trop. Med. Hyg., 2018, 99(2), 256-265.
[http://dx.doi.org/10.4269/ajtmh.17-0889] [PMID: 29968557]
[8]
Enderle, Y.; Foerster, K.; Burhenne, J. Clinical feasibility of dried blood spots: Analytics, validation, and applications. J. Pharm. Biomed. Anal., 2016, 130, 231-243.
[http://dx.doi.org/10.1016/j.jpba.2016.06.026] [PMID: 27390013]
[9]
Freeman, J.D.; Rosman, L.M.; Ratcliff, J.D.; Strickland, P.T.; Graham, D.R.; Silbergeld, E.K. State of the science of dried blood spots. Clin. Chem., 2018, 64(4), 656-679.
[http://dx.doi.org/10.1373/clinchem.2017.275966] [PMID: 29187355]
[10]
Brindle, E.; Lillis, L.; Barney, R.; Bansil, P.; Lyman, C.; Boyle, D.S. Measurement of micronutrient deficiency associated biomarkers in dried blood spots using a multiplexed immunoarray. PLoS One, 2019, 14(1)e0210212
[http://dx.doi.org/10.1371/journal.pone.0210212] [PMID: 30620768]
[11]
Sulochana, S.P.; Daram, P.; Srinivas, N.R.; Mullangi, R. Review of DBS methods as a quantitative tool for anticancer drugs. Biomed. Chromatogr., 2019, 33(1)e4445
[http://dx.doi.org/10.1002/bmc.4445] [PMID: 30512220]
[12]
US DHHS FDA, CDER, CVM. Guidance for Industry: Bioanalytical Method Validation. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Veterinary Medicine. CVM: Rockville, MD, USA 2018.
[13]
Dittakavi, S.; Jat, R.K.; Mullangi, R. Quantitation of ivosidenib, a novel mutant IDH1 inhibitor on mice DBS: Application to a pharmacokinetic study. Drug Res. (Stuttg.), 2019, 69(9)
[14]
Dittakavi, S.; Jat, R.K.; Mullangi, R. Quantitative analysis of enasidenib in dried blood spots of mouse blood using an increased-sensitivity LC-MS/MS method: Application to a pharmacokinetic study. Biomed. Chromatogr., 2019, 33(6)e4491
[http://dx.doi.org/10.1002/bmc.4491] [PMID: 30663096]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy