In this paper we show the application of the Tasso OnDemand™, a novel automated sample collection device, in conjunction with volumetric absorptive microsampling (VAMS) for the development of gefapixant, a P2X3 receptor antagonist currently under clinical development for the treatment of refractory and unexplained chronic cough and endometriosis-related pain. A LC–MS/MS bioanalytical method was developed and validated using VAMS to support this development program. This method was utilized in a drug–drug interaction study to establish a mathematical bridging relationship with data obtained from a validated plasma assay used to support the program. The VAMS bioanalytical method and the predictability of the mathematical relationship is reported and discussed here.
Absfracf -ST68 is a surfactant based contrast agent being used to enhance diagnostic ultrasound imaging as well as develop a technique for targeting. The sue of the ST68 nanohnbhles is being reduced in order to facilitate passage through tumor blood vessel pores. Different sonication times are being investigated in order to determine the smallest s e of the nanobuhhles. The contrast agent is characterized hy dynamic light scattering and acoustic dose response to develop the maximum enhancement.
This paper describes an automated workflow for the determination of selected reaction monitoring (SRM) transitions and optimum mass spectrometric (MS) instrument parameters. The approach uses a Nanomate from Advion Biosciences for automated infusion of small amounts of sample in combination with Automaton optimization software from Sciex. The results are stored in the Analyst software Compound Database for automated acquisition method building. Comparisons are presented between the more traditional optimization methods of manual flow injection optimization, Autotune infusion optimization, Automaton flow injection optimization and the Nanomate-Automaton optimization approach. Data is also presented to show that acquisition methods developed on the Sciex model API3000 instrument can be effectively transferred to the Sceix API4000 and API5000 model instruments.
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