Stabilometry in patients with Dravet Syndrome to quantitatively assess ataxia: A preliminary study
Gait & Posture(2018)
Abstract
CT-707, a mutant-selective inhibitor of an important cancer target, anaplastic lymphoma kinase (ALK), is designed to be a targeted therapeutic agent for non-small cell lung cancer (NSCLC) patients harboring ALK active and crizotinib resistant mutations. A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) method was developed and validated for the determination of CT-707 and its two metabolites (M1 and M2) in human plasma. The samples were purified by solid phase extraction (SPE) and separated on a BEH C18 column (2.1 × 50 mm, 1.7 μm). Electrospray ionization (ESI) in positive ion mode and multiple reactions monitoring (MRM) were used to monitor the ion transitions at m/z 636.4+ → 413.3+, 594.4+ → 494.4+, 622.5+ → 536.4+, respectively. The results indicated that the method had excellent sensitivity and selectivity. The linear range covered from 2 to 500 ng/mL for CT-707and from 1 to 100 ng/mL for M1 and M2. Intra-run and inter-run precisions (in terms of %RSD) were all <15% and the accuracies (in terms of %RE) were within the range of ±15%. The lower limit of quantification (LLOQ), matrix effect, extraction recovery, stability, dilution test and carryover test were also validated and satisfied with the criteria of validation. Finally, the method was successfully applied to a phase I clinical study of ALK-positive advanced NSCLC patients after an oral administration of CT-707.
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Key words
ALK Inhibitors
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