Development and validation of a liquid chromatography-mass spectrometry (LC-MS) assay for the determination of the anti-cancer agent N-[2-(dimethylamino)ethyl]-2,6-dimethyl-1-oxo-1,2-dihydrobenzo[b]-1,6-naphthyridine-4-carboxamide (SN 28049)

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Abstract

N-[2-(Dimethylamino)ethyl]-2,6-dimethyl-1-oxo-1,2-dihydrobenzo[b]-1,6-naphthyridine-4-carboxamide (SN 28049) is a potent topoisomerase II poison being developed to treat solid tumours. A reliable and sensitive LC-MS method has been developed and validated for the determination of SN 28049 in plasma using a structurally similar internal standard. This method had acceptable intra- and inter-assay accuracy (95-105%) and precision (R.S.D. < 6.5%) over the range 0.062-2.5 μM (using a 100 μl sample), and had a lower limit of quantitation of 0.062 μM. Both aqueous and plasma solutions of SN 28049 were stable during short-term (24 h at room temperature or 4 °C) and long-term storage (8 months at -80 °C), and following freezing and thawing (three cycles). The method was applied to study the pharmacokinetics of SN 28049 in mice after iv administration (8.9 mg/kg; n = 3 mice per time point). The maximum plasma concentration achieved was 1.22 ± 0.05 μM, and concentrations were measurable up to 12 h post-administration. A bi-exponential concentration-time curve was observed with an elimination half-life of 2.3 ± 0.2 h (mean ± S.E.), a volume of distribution of 34.5 ± 2.2 l/kg, and a plasma clearance of 12 ± 0.5 l/h/kg. © 2008 Elsevier B.V. All rights reserved.

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Lukka, P. B., Kestell, P., Paxton, J. W., & Baguley, B. C. (2008). Development and validation of a liquid chromatography-mass spectrometry (LC-MS) assay for the determination of the anti-cancer agent N-[2-(dimethylamino)ethyl]-2,6-dimethyl-1-oxo-1,2-dihydrobenzo[b]-1,6-naphthyridine-4-carboxamide (SN 28049). Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 875(2), 368–372. https://doi.org/10.1016/j.jchromb.2008.09.023

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