Development and validation of a sensitive and selective LC—MS/MS method for the determination of an antimalarial drug candidate in rat plasma, and its application to a preclinical pharmacokinetic study

• Autorzy: Pires C. , Kaiser M. , Grünspan L. D. , Barreto F. , Innocente A. , Gnoatto S. , Laureano J. V. , Araujo B. , Costa T. , Tasso L.
• Języki publikacji: EN

Abstrakty

EN

An accurate and reliable LC—MS/MS assay was firstly developed and validated for quantitative determination of a new antimalarial prototype drug, 3β-hydroxyurs-12-en-28-oic acid (LAFIS 01), in rat plasma. Dexamethasone was employed as internal standard. Simple protein precipitation by acetonitrile for the sample preparation was used. Effective separation was achieved with Phenomenex Luna C18 (50 × 2 mm, 5 μm) column. The mobile phase consisted of (A) water and (B) acetonitrile, both containing 0.1% acetic acid, delivered by gradient elution. The column temperature was maintained at 40 °C. The LAFIS 01 was monitored by electrospray ionization interface, operating in the negative mode (ESI−) in multiple reactions monitoring (MRM), checking the transitions 455 > 455 for LAFIS 01 and 451 > 361 for the IS. Once LAFIS 01 demonstrated low fragmentation by collision-induced dissociation (CID) nonpresenting abundant high-intensity fragments to meet the desired concentration levels quantification, only pseudomolecular ion was monitored. The flow rate was 500 μL min−1. The lower limit of quantitation achieved was 10 ng mL−1 and linearity was observed from 10 to 500 ng mL−1. The relative standard deviation (RSD) values of the intra- and inter-assay precisions of the method were below 8.42 and 7.94%, respectively. The accuracy ranged from 92.05 to 102.94%. The extraction recovery of LAFIS 01 and IS was up to 90%. The method showed linearity, precision, accuracy, sensitivity, and stability required to quantify LAFIS 01 in preclinical pharmacokinetic study.

Słowa kluczowe

EN

LAFIS 01; antimalarial; LC-MS/MS; preclinical pharmacokinetics

• Wydawca: University of Silesia in Katowice ; Akademiai Kiado
• Czasopismo: Acta Chromatographica
• Rocznik: 2016
• Tom: Vol. 28, no. 4
• Strony: 439--453
• Opis fizyczny: Bibliogr. 13 poz., rys.

Twórcy

autor

Pires C.

• Laboratory of Pharmacology, College of Pharmacy, University of Caxias do Sul, RS, Brazil

autor

Kaiser M.

• Post-Graduate Program in Pharmaceutical Sciences, College of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

autor

Grünspan L. D.

• Post-Graduate Program in Biotecnology, University of Caxias do Sul, Caxias do Sul, RS, Brazil

autor

Barreto F.

• Post-Graduate Program in Pharmaceutical Sciences, College of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

autor

Innocente A.

• Post-Graduate Program in Pharmaceutical Sciences, College of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

autor

Gnoatto S.

• Post-Graduate Program in Pharmaceutical Sciences, College of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

autor

Laureano J. V.

• Post-Graduate Program in Pharmaceutical Sciences, College of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

autor

Araujo B.

• Post-Graduate Program in Pharmaceutical Sciences, College of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

autor

Costa T.

• Post-Graduate Program in Pharmaceutical Sciences, College of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

autor

Tasso L.

Bibliografia

• [1] WHO, World Malaria Report, Geneva, 2013
• [2] I. Petersen, R. Eastman, and M. Lanzer, FEBS Lett., 585, 1551–1562 (2011)
• [3] T. Mita, K. Tanabe, and K. Kita, Parasitol Int., 5, 201–209 (2009)
• [4] Q. Cheng, D.E. Kyle, and M.L. Gatton, Int. J. Parasitol, 2, 249–255 (2012)
• [5] D.A. Fidock, P.J. Rosenthal, S.L. Croft, R. Brun, and S. Nwaka, Nature Rev., 3, 509–520 (2001)
• [6] J. Wiesner and H. Jomaa, Curr. Drug Targ., 8, 3–13 (2007)
• [7] M.N. Aminake, S. Shoof, L. Sologub, M. Leubner, M. Kirschner, A. Hans-Dieter, and G. Pradel, Antimicrob. Agents Chemother., 55, 1338–1348 (2011)
• [8] S.C.B. Gnoatto, S. Susplugas, L. Dalla Vechia, T.B. Ferreira, A. Dassonville-Klimpt, K.R. Zimmer, C. Demailly, S. Nascimento, J. Guillon, P. Grellier, H. Verli, G. Gosmann, and P. Sonnet, Bioorg. Med. Chem., 16, 771–782 (2008)
• [9] A.M. Innocente, G.N.S. Silva, L.N. Cruz, M.S. Moraes, M. Nakabashi, P. Sonnet, G. Gosmann, C.R.S. Garcia, and S.C.B. Gnoatto, Molecules, 17, 12003–12014 (2012)
• [10] US Food and Drug Administration, Center for Drug Evaluation and Research, US Food and Drug Administration, Center for Drug Evaluation and Research, 2001. http://www.fda.gov/downloads/Drugs/Guidance/ComplianceRegulatoryInfor mation/Guidances/UCM070107.pdf
• [11] L. Shargel, S. Wu-Pong, and A.B.C. Yu, Applied Biopharmaceutics and Pharmacokinetics, 5th edn., McGraw-Hill Book Co., New York, NY, 2005
• [12] M. Gibaldi and D. Perrier, Pharmacokinetics, 2nd edn., Marcel Dekker, New York, NY, 1982
• [13] L. Zhang, M. Yu-Liang, L. Yang, and Z.J. Yuan-Gang, Chromatogr. B., 963, 62–69 (2014)

Uwagi

PL

Opracowanie ze środków MNiSW w ramach umowy 812/P-DUN/2016 na działalność upowszechniającą naukę.