title: Development and validation of a liquid chromatography-ultraviolet absorbance detection assay using derivatisation for the novel marine anticancer agent ES-285 x HCl [(2S,3R)-2-amino-3-octadecanol hydrochloride] and its pharmaceutical dosage form.
abstract: ES-285 x 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 x HCl warranted the availability of an assay for the quantification and purity determination of ES-285 x HCl active pharmaceutical ingredient (API) and its pharmaceutical dosage form. A liquid chromatographic method (LC) comprising of derivatisation of ES-285 x 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 x 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.
authors.affiliation: Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Slotervaart Hospital, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. apmbk@slz.nl
authors.forename: Monique W J
authors.initials: MW
authors.lastname: den Brok
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Nuijen
authors.forename: Elena
authors.initials: E
authors.lastname: Miranda
authors.forename: Pablo
authors.initials: P
authors.lastname: Floriano
authors.forename: Simon
authors.initials: S
authors.lastname: Munt
authors.forename: Ignacio
authors.initials: I
authors.lastname: Manzanares
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000473:Alkanes / Q000032:analysis*; D000970:Antineoplastic Agents / Q000032:analysis*; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D008055:Lipids / Q000032:analysis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
chemical_list: D000473:Alkanes; D000970:Antineoplastic Agents; D008055:Lipids; C408363:spisulosine