title: Validation of high-performance liquid chromatography-tandem mass spectrometry assays for the quantification of eribulin (E7389) in various biological matrices.
abstract: This paper presents specific and sensitive high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) assays for the quantification of the novel anticancer agent eribulin in human plasma, whole blood, urine and faeces. These assays, developed to support clinical pharmacological studies with the drug, quantify eribulin concentration ranges of 0.2-100ng/mL for plasma, 0.5-100 ng/mL for whole blood and urine and 0.1-25 μg/g for faeces, using sample volumes of 500 μL or 250 μg (faeces). Samples were prepared with liquid-liquid extraction, separated on a C18 column with gradient elution and analysed with a triple quadrupole MS, in positive ion mode. A structural analogue of eribulin was used as internal standard for the quantification. The assays were linear with correlation coefficients (r(2)) of 0.99 and better, whereby the deviation from nominal concentrations ranged from -8.2 to 8.9% with CV values of maximally 14.2%. Stability assessments demonstrated that eribulin is stable at -20°C in plasma, whole blood, urine and faeces for at least 38, 4, 10.5 and 5 months, respectively. In conclusion, the validation results show that the assays are specific and accurate and can therefore adequately be applied to support clinical studies of eribulin.
authors: Department of Clinical Pharmacology, Slotervaart Hospital, The Netherlands Cancer Institute, Amsterdam, The Netherlands. anne-charlotte.dubbelman@slz.nl
authors: A C
authors: AC
authors: Dubbelman
authors: H
authors: H
authors: Rosing
authors: B
authors: B
authors: Thijssen
authors: L
authors: L
authors: Lucas
authors: W
authors: W
authors: Copalu
authors: J
authors: J
authors: Wanders
authors: J H M
authors: JH
authors: Schellens
authors: J H
authors: JH
authors: Beijnen
mesh_terms: D005591:Chemical Fractionation; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005243:Feces / Q000737:chemistry*; D005663:Furans / Q000032:analysis* / Q000097:blood / Q000652:urine; D006801:Humans; D007659:Ketones / Q000032:analysis* / Q000097:blood / Q000652:urine; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000095662:Polyether Polyketides
chemical_list: D005663:Furans; D007659:Ketones; C490954:eribulin; D000095662:Polyether Polyketides