Development and validation of a liquid chromatography-ultraviolet absorbance detection assay using derivatisation for the novel marine anticancer agent ES-285-HCl [(2S,3R)-2-amino-3-octadecanol hydrochloride] and its pharmaceutical dosage form

Den Brok, MWJ; Nuijen, B; Miranda, E; Floriano, P; Munt, S; Manzanares, I; Beijnen, JH

HERO ID

4936592

Reference Type

Journal Article

Year

2003

HERO ID 4936592
In Press No
Year 2003
Title Development and validation of a liquid chromatography-ultraviolet absorbance detection assay using derivatisation for the novel marine anticancer agent ES-285-HCl [(2S,3R)-2-amino-3-octadecanol hydrochloride] and its pharmaceutical dosage form
Authors Den Brok, MWJ; Nuijen, B; Miranda, E; Floriano, P; Munt, S; Manzanares, I; Beijnen, JH
Journal Journal of Chromatography A
Volume 1020
Issue 2
Page Numbers 251-258
Abstract ES-285(.)HCl [(2S,3R)-2-amino-3-octadecanol hydrochloride] is a novel investigational anticancer agent, which has shown in vitro and in vivo cytotoxic activity against various tumor cell lines with selectivity for certain solid tumors. The pharmaceutical development of ES-285(.)HCl warranted the availability of an assay for the quantification and purity determination of ES-285(.)HCl active pharmaceutical ingredient (API) and its pharmaceutical dosage form. A liquid chromatographic method (LC) comprising of derivatisation of ES-285(.)HCl with phenylisothiocyanate and UV-detection was developed. The method was found to be linear, precise and accurate. The assay also proved selectivity as determined by analysing ES-285(.)HCl in combination with 15 analogues and in combination with hydroxypropyl-beta-cyclodextrin, the excipient used in the lyophilised pharmaceutical dosage form. Stress testing showed that the degradation products were separated from the parent compound, confirming its stability indicating capacity. The method was found robust as determined with design of experiments (DoE), which made it possible to predict system suitability responses in worst case experimental conditions and to define criteria for system suitability testing. (C) 2003 Elsevier B.V. All rights reserved.
Doi 10.1016/j.chroma.2003.08.094
Wosid WOS:000186557300009
Is Certified Translation No
Dupe Override No
Is Public Yes
Keyword derivatisation; LC; design of experiments; (2S,3R)-2-ainino-3-octadecanol hydrochloride; phenylisothiocyanate; ES-285-HCl