Highly sensitive UHPLC—MS/MS method for quantification of ethylenediamine-N,N′-di-2-(3-cyclohexyl) propanoic acid derivatives in mouse serum

• Autorzy: Tubić B. K. , Marković B. D. , Vladimirov S. S. , Ristić S. M. , Ivković B. M. , Savić M. M. , Poljarević J. M. , Sabo T. J.

Identyfikatory

DOI

10.1556/1326.2017.29.2.7

• Języki publikacji: EN

Abstrakty

EN

A series of new (S,S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoate esters has shown cytotoxic activity towards human leukemic cell lines. The aim of this study was to develop and validate a bioanalytical method for quantification of (S,S)-O,O-diethyl-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoate dihydrochlorides (DE-EDCP) and its metabolite, substituted propanoic acid (EDCP), in mouse serum by ultra high-performance liquid chromatography—tandem mass spectrometry (UHPLC—MS/MS). Structural analog, derivative of 1,3-propanediamine, was used as an internal standard (IS). Sample preparation employed protein precipitation by acetonitrile and subsequent centrifugation. Optimal UHPLC separation conditions were set to achieve simultaneous determination of both compounds in a short run time of 6 min. Additionally, the selected reaction monitoring (SRM) mode developed in this method allowed a highly sensitive, accurate, and precise identification of compounds of interest. The lower limit of quantitation (LOQ) was 1.3 ng mL−1 for DE-EDCP and 0.3 μg mL−1 for EDCP. The calibration curves were linear over the concentration range of 1.3–26.7 ng mL−1 and 0.3–6.7 μg mL−1 for DE-EDCP and EDCP, respectively. Precision (%CV) and accuracy (%RE) for DE-EDCP and EDCP ranged from 3.5% to 16.0% and from 1.8% to 14.4%, respectively. The validation process was performed in accordance with the regulatory guidance/guideline, and all of the obtained results met the established acceptance criteria. The newly developed and validated UHPLC—MS/MS method is rapid, sensitive, and selective, and it can be successfully applied to drug monitoring in nonclinical studies.

Słowa kluczowe

EN

UHPLC—MS/MS; protein precipitation sample preparation; (S S)-ethylenediamine-N; N′-di-2-(3-cyclohexyl) propanoic acid esters; cytotoxic activity

• Wydawca: University of Silesia in Katowice ; Akademiai Kiado
• Czasopismo: Acta Chromatographica
• Rocznik: 2017
• Tom: Vol. 29, no. 2
• Strony: 235--252
• Opis fizyczny: Bibliogr. 14 poz., rys.

Twórcy

autor

Tubić B. K.

• Agency for Medicines and Medical Devices of Bosnia and Herzegovina, St. Veljka Mlađenovića bb, 78000 Banjaluka, Bosnia and Herzegovina

autor

Marković B. D.

• Faculty of Pharmacy, University of Belgrade, St. Vojvode Stepe 450, 11040 Belgrade, Republic of Serbia

autor

Vladimirov S. S.

• Faculty of Pharmacy, University of Belgrade, St. Vojvode Stepe 450, 11040 Belgrade, Republic of Serbia

autor

Ristić S. M.

• Galenika a.d., Institute for Research and Development, St. Pasterova 2, 11000 Belgrade, Republic of Serbia

autor

Ivković B. M.

• Faculty of Pharmacy, University of Belgrade, St. Vojvode Stepe 450, 11040 Belgrade, Republic of Serbia

autor

Savić M. M.

• Faculty of Pharmacy, University of Belgrade, St. Vojvode Stepe 450, 11040 Belgrade, Republic of Serbia

autor

Poljarević J. M.

• Faculty of Chemistry, University of Belgrade, St. Studentski trg 12-16, 11000 Belgrade, Republic of Serbia

autor

Sabo T. J.

• Faculty of Chemistry, University of Belgrade, St. Studentski trg 12-16, 11000 Belgrade, Republic of Serbia

Bibliografia

• [1] S. Misirlic Dencic, J. Poljrević, U. Vilimanovich, A. Bogdanovic, A.J. Isakovic, T. Kravic Stevovic, M. Dulovic, N. Zogovic, A.M. Isakovic, S. Grguric-Sipka, V. Bumbasirevic, T. Sabo, V. Trajkovic, and I. Markovic, Chem. Res. Toxicol., 25, 931 (2012)
• [2] M.N. Zahir, N. Masood, and M. Shabbir-Moosajee, J. Med. Case Rep., 6, 409 (2012)
• [3] R.A. Alderden, M.D. Hall, and T.W. Hambley, J. Chem. Educ., 83, 728, (2006)
• [4] E. Estrada, E. Uriarte, A. Montero, M. Teijeira, L. Santana, and E. De Clercq, J Med Chem., 43, 1975 (2000)
• [5] M.J. Lazić, L. Vucićević, S. Grgurić-Sipka, K. Janjetović, N.G. Kaluderović, M. Misirkić, M. Gruden-Pavlović, D. Popadić, R. Paschke, V. Trajković, and T.J. Sabo, ChemMedChem, 5, 881 (2010)
• [6] FDA, Guidance for Industry: Bioanalytical Method Validation, 2001
• [7] EMA, Guideline on Bioanalytical Method Validation, 2011
• [8] R.A. Dean, C.D. Christian, R.H. Barray Sample, and W.F. Bosron, FASEB J., 5, 2735 (1991)
• [9] V.M. Djinović, V.V. Glodjović, G.P. Vasić, V. Trajković, O. Klisurić, S. Stanković, T.J. Sabo, and S.R. Trifunović, Polyhedron, 29, 1933 (2010)
• [10] B.B. Krajčinović, G.N. Kaluđerović, D. Steinborn, H. Schmidt, C. Wagner, Ž. Žižak, Z.D. Juranić, S.R. Trifunović, and T.J. Sabo, J. Inorg. Biochem., 102, 892 (2008)
• [11] Lj.E. Mihajlović, A. Savić, J. Poljarević, I. Vučković, M. Mojić, M. Bulatović, D. Maksimović-Ivanić, S. Mijatović, G.N. Kaluđerović, S. Stošić-Grujičić, Đ. Miljković, S. Grgurić-Šipka, and T.J. Sabo, J. Inorg. Biochem., 109, 40 (2012)
• [12] Dj. Miljković, J.M. Poljarević, F. Petković, J. Blaževski, M. Momčilović, I. Nikolić, T. Saksida, S. Stošic-Grujičić, S. Grgurić-Šipka, and T.J. Sabo, Eur. J. Med. Chem., 47, 194 (2012)
• [13] S. Lakshmana Prabu and T.N.K. Suriyaprakash, Applied Biological Engineering — Principles and Practice. In: Dr.Ganesh R. Naik (Ed.), Extraction of Drug from the Biological Matrix: A Review, In Tech, 2012. pp. 485
• [14] L. Jia, J.E. Tomaszewski, P.E. Noker, G.S. Gorman, E. Glaze, and M. Protopopova, J. Pharm. Biomed. Anal., 37, 793 (2005).

Uwagi

PL

Opracowanie ze środków MNiSW w ramach umowy 812/P-DUN/2016 na działalność upowszechniającą naukę (zadania 2017).