CARRS screen

Mei et al. (2006) demonstrated that the CARRS screen could be used to predict rat oral bioavailability and was therefore a useful in vivo discovery screen. 

Carr LG, Foroud T, Bice P et al. Mapping of a quantitative locus for alcohol consumption in selectively bred rat lines. Alcohol Clin Exp Res 1998 22 884-887. Bice P, Foroud T, Bo R et al. Genomic screen for QTLs underlying alcohol consumption in the P and NP rat lines. Mamm Genome 1998 9 949-955. 

Carr, R. Jhoti, H. Structure-based screening of low-affinity compounds. Drug Disc. Today 2002, 7, 522-527. 

Liu, J., Carr, S., Rinaldi, K., Chandler, W. Screening estrogenic oxidized byproducts by combining ER binding... 

In-vitro Microsomal Stability Screen Caco-2 Absorption Screen P450 Enzyme Inhibition Screen Rapid Rat" (CARRS) PO/PK Screen... 

The rules for level I (screening) assays are shown in Table 13.1. An example of the type of samples where a level I assay could be used is the CARRS samples [85] that can be used for screening NCEs using a rat PK model [vide supra). The concept behind this assay is that it should use a small number of standards and a simple linear extrapolation. For level II assays (see Table 13.2) that might be used for discovery PK studies in preclinical species, a complete standard curve is required. In this case a complete standard curve is defined as 10-15 standards in duplicate assayed with at least five standards used in the final calibration curve. Neither level I nor level II assays require the use of quality control (QC) standards. When a compound is in the lead qualification stage, then a level III assay would be required. As shown in Table 13.3, the main distinction for level III assays is that they are required to include at least six QC standards. As described in Tables 13.1-13.3, these rules show the requirements for how an assay should be set up before the samples are assayed and then these rules describe the acceptance criteria for the assays after they have been performed. 

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)...

Carr et al., 1993). The neutral loss scan mode is used as a class identifier to also screen components that contain a common substructure. Barbuch et al. demonstrated this approach for the class identification of phytoestrogens (Barbuch et al., 1989), using thermospray ionization (TSI)-LC/MS/MS. Brownsill et al. used a similar electrospray ionization (ESI)-LC/MS/MS approach for the analysis of metabolites in rat liver slices (Brownsill et al., 1994). 

Similar analysis strategies are applied for the peptide mapping of glycoproteins (Medzihradszky et al., 1994 Reinhold et al., 1995 Hancock et al., 1996). Carr and co-workers combined in-source col-lisionally induced dissociation (CID) with LC/MS/MS to identify sites of N- and O-linked glycosylation (Carr et al., 1993). This novel approach uses a series of LC/MS and LC/MS/MS experiments to generate peptide maps and to selectively screen for glycoproteins. 

Summary of the data obtained for 30 compounds screened using the CARRS assay ... 

Adapted from Marmor MF, Carr RE, Easterbrook M, et al. Recommendations on screening for chloroqnine and hydroxychloroquine retinopathy a report by the American Academy of Ophthalmology. Ophthalmology 2002 109 1377-1382. 

Optional) Inlet strainer screening for inclusion into reservoir and as cover for reservoir top as well McMaster- Carr See catalog for at least 40 mesh ... 

Stoner, T.J., B. Down, W.P. Carr, G. Maldonado, T.R. Church, and J. Mandel 1998. "Do Vouchers Improve Breast Cancer Screening Rates Results from a Randomized Trial." Health ServRes 331 11-28. 

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. 

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