Cassette Accelerated Rapid Rat Screen

Another approach that has been developed to streamline and standardize the PK screening activities is known as CARRS [63], This approach was developed by Korfmacher and coworkers and uses a 96-well plate that accommodates a total of six compounds dosed via single compound administration. One compound is dosed per rat and two rats are used per drug candidate. Plasma samples are collected at six time points resulting in a set of 12 rat plasma samples. The plasma samples are then pooled across time points for each rat resulting in a total of six pooled samples (i.e., one sample per time point). An abbreviated three-point calibration curve is used for each assay. 

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There are a number of solutions that have been proposed to address the limitations on throughput in PK assays, including cassette dosing [37], where typically five compounds are dosed in a mixture, pooling of plasma samples from multiple animals receiving a specific dose, or the cassette-accelerated rapid rat screen where the processing of samples is streamlined [38]. 

K. J. Veals, J. Hsieh, Y. etal. Cassette-accelerated rapid rat screen a systematic procedure for the dosing and liquid chromatography/ atmospheric pressure ionization tandem mass spectrometric analysis of new chemical entities as part of new drug discovery. Rapid Commun Mass Spectrom 2001, 15, 335-340. 

Figure 1.4. NCE/NME progression scheme showing the various discovery stage liquid chromatography-mass spectrometry (LC-MS) and LC-tandem MS (LC-MS/MS) assays used for selecting NME/NCE to advance into development. (Reprinted with permission from Korfmacher, 2005.) (CARRS, Cassette accelerated rapid rat screening IV, Intravenous administration PO, Oral administration NCE, New chemical entity)...

Korfmacher and co-workers have increased efficiency through streamlined and standardized rehnement of the bioanalytical process [119]. Their approach, known as cassette-accelerated rapid rat screen (CARRS), is based around a 96-well template that accommodates six compounds dosed via single-compound administration. Higher efficiency is achieved through the use of abbreviated standard curve.s (25, 250, and 2500 ng/mL), time points that are pooled from multiple animals, and the use of a standardized format. 

Korfmacher, W.A. Cox, K.A. Ng, K.J. Veals, J. Hsieh, Y. Wainhaus, S. Broske, L. Prelusky, D. Nomeir, A. White, R.E. Cassette-Accelerated Rapid Rat Screen A Systematic Procedure for the Dosing and Liquid Chromatography/Atmospheric Pressure Ionization TandemMass Spectrometric Analysis of New Chemical Entities as Part of New Drug Discovery, Rapid Commun. Mass Spectrom. 15, 335-340 (2001). 

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