Risperidone immunoassay
Inventors
Salamone, Salvatore J. • Courtney, Jodi Blake • Cline, Daniel J. • Sard, Howard • Hegde, Vishnumurthy
Assignees
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Publication Number
US-8088594-B2
Publication Date
2012-01-03
Expiration Date
Abstract
Novel conjugates and immunogens derived from risperidone and antibodies generated by these immunogens are useful in immunoassays for the quantification and monitoring of risperidone and paliperidone in biological fluids.
Core Innovation
The invention provides an immunoassay for detecting active pharmaceutically anti-psychotic drugs selected from risperidone, paliperidone and mixtures thereof by using an antibody that selectively reacts with the active drugs and shows little substantial reactivity with pharmacologically inactive risperidone and paliperidone metabolites. The immunoassay uses a conjugate of a carrier with a ligand having a specified chemical formula including variables B, Y, X, and p. Detection is carried out by causing the pharmaceutically active anti-psychotic drug in a sample to bind with the antibody together with the conjugate, followed by measuring the amount of conjugate that is bound or unbound to the antibody.
The antibody is characterized by reactivity and cross reactivity constraints with specific metabolites. Reactivity with 7-hydroxy-risperidone is less than 40%, and cross reactivity with other pharmacologically inactive risperidone and paliperidone metabolites is less than 5%, where the reactivity and cross reactivity are based upon the antibody’s combined reactivity with both risperidone and paliperidone. The immunoassay thereby enables detection of the presence of anti-psychotic drugs in a sample using selective antibody recognition of the active drugs relative to inactive metabolite reactivity.
The documented embodiments describe forming risperidone acid derivative ligands and converting them to s-NHS activated esters for protein conjugation to prepare KLH and BSA immunogens/conjugates. Antibodies directed to risperidone are generated to provide polyclonal and monoclonal anti-risperidone antibodies, and an indirect competitive microtiter-plate ELISA format is used to test cross-reactivity.
Claims Coverage
The patent document includes two independent claims that cover an immunoassay and a kit, each centered on a selectively reactive antibody and a carrier-ligand conjugate defined by B, Y, X, and p, with reactivity constraints against inactive metabolites. Across the independent claims, there are two main inventive feature groupings: the immunoassay format and the kit packaging of separate reagents using the same selective binding system.
Selective antibody-based immunoassay for risperidone and paliperidone detection
An immunoassay for detecting active pharmaceutically anti-psychotic drugs selected from risperidone, paliperidone and mixtures thereof, comprising a sample, a conjugate of a carrier with a ligand having B, Y, X and p, and an antibody selectively reactive with said drugs having little substantial reactivity with pharmacologically inactive metabolites 7-hydroxy-risperidone and other inactive metabolites, with reactivity with 7-hydroxy-risperidone less than 40% and cross reactivity with other inactive metabolites less than 5%; detection is by measuring the amount of conjugate bound or unbound to the antibody.
Packaged kit with conjugate reagent and selective antibody for patient-sample detection
A kit for determining the presence of pharmaceutical active anti-psychotic drugs selected from risperidone and paliperidone in a patient sample comprising separate reagents in separate containers, including a conjugate of a carrier with a ligand having B, Y, X and p, and an antibody selectively reactive with risperidone and paliperidone, with little substantial reactivity with 7-hydroxy-risperidone and other pharmacologically inactive metabolites, with reactivity with 7-hydroxy-risperidone less than 40% and cross reactivity with other inactive metabolites less than 5%.
The claims are directed to a selective antibody and a carrier-ligand conjugate system defined by B, Y, X, and p, used either as an immunoassay that measures bound versus unbound conjugate or as a kit containing separate reagents. Both independent claims require limited reactivity with 7-hydroxy-risperidone and limited cross reactivity with other inactive metabolites.
Stated Advantages
The antibody has little substantial reactivity with the pharmacologically inactive metabolite 7-hydroxy-risperidone.
The antibody has no substantial cross-reactivity with other pharmacologically inactive risperidone and paliperidone metabolites.
Reactivity with 7-hydroxy-risperidone is less than 40% and cross reactivity with other inactive metabolites is less than 5%.
The conjugate binding measurement of bound or unbound conjugate enables detection of the presence of risperidone and/or paliperidone in the sample.
Substantially responsive detection of risperidone (active form) and paliperidone.
Low cross-reactivity with pharmacologically inactive risperidone and paliperidone metabolites, including 7-hydroxy-risperidone and N-dealkyl-risperidone.
Documented Applications
Therapeutic drug management by detecting active pharmaceutically anti-psychotic drugs selected from risperidone, paliperidone, and mixtures thereof in human biological fluids (patient sample).
Indirect competitive microtiter plate ELISA immunoassay format for determining cross-reactivity using risperidone-BSA coatings and determining IC50 values.
Use of the generated polyclonal and monoclonal anti-risperidone antibodies to evaluate responsiveness to risperidone and paliperidone and cross-reactivity to inactive metabolites.
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