Antibodies to aripiprazole haptens and use thereof
Disclosed is an antibody which binds to aripiprazole, which can be used to detect aripiprazole in a sample such as in a competitive immunoassay method. The antibody can be used in a lateral flow assay device for point-of-care detection of aripiprazole, including multiplex detection of aripiprazole, olanzapine, quetiapine, and risperidone in a single lateral flow assay device.
1. A method of detecting aripiprazole in a sample, the method comprising:
(i) selecting a host for antibody production;
(ii) inoculating the host with a conjugate of a compound of Formula I and an immunogenic carrier, wherein the host generates an antibody or a binding fragment thereof that specifically binds to aripiprazole,
wherein:
the immunogenic carrier is linked to the substituent at the R 1 position of the compound of Formula I,
R 1 is
R 2 is H;
R 3 is H; and
m is 1, 2, 3, 4, or 5;
(iii) isolating the antibody or the binding fragment thereof that specifically binds to aripiprazole;
(iv) labeling the antibody and/or the binding fragment thereof with a detectable maker;
(v) contacting a sample with the antibody or the binding fragment thereof labeled with the detectable marker, wherein the labeled antibody or the labeled binding fragment and aripiprazole present in the sample form a labeled complex; and
(vi) detecting the labeled complex so as to detect aripiprazole in the sample.
2. A competitive immunoassay method for detecting aripiprazole in a sample, the method comprising:
(i) selecting a host for antibody production;
(ii) inoculating the host with a conjugate of a compound of Formula I and an immunogenic carrier, wherein the host generates an antibody or a binding fragment thereof that specifically binds to aripiprazole,
wherein:
the immunogenic carrier is linked to substituent at the R 1 position of the compound of Formula I,
R 1 is
R 2 is H;
R 3 is H; and
m is 1, 2, 3, 4, or 5;
(iii) isolating the antibody or the binding fragment thereof that specifically binds to aripiprazole;
(iv) labeling the antibody and/or the binding fragment thereof with a detectable maker;
(v) contacting the sample with the antibody or the binding fragment thereof, and with aripiprazole or a competitive binding partner of aripiprazole, wherein sample aripiprazole competes with the aripiprazole or the competitive binding partner thereof for binding to the antibody or the binding fragment thereof; and
(vi) detecting the detectable marker so as to detect the sample aripiprazole.
3. The method of claim 2 wherein the aripiprazole or competitive binding partner thereof is labeled with the detectable marker.
4. The method of claim 2 wherein the antibody is labeled with a detectable marker.
5. The method of claim 2 wherein the immunoassay is performed on a lateral flow assay device and the sample is applied to the device.
6. The method of claim 1 , further comprising detecting the presence of one or more analytes in addition to aripiprazole.
7. The method of claim 6 , wherein the one or more analytes are anti-psychotic drugs other than aripiprazole.
8. The method of claim 7 , wherein the anti-psychotic drugs other than aripiprazole are selected from the group consisting of: risperidone, paliperidone, quetiapine, olanzapine, and metabolites thereof.
9. The method of claim 2 , further comprising detecting the presence of one or more analytes in addition to aripiprazole.
10. The method of claim 9 , wherein the one or more analytes are anti-psychotic drugs other than aripiprazole.
11. The method of claim 10 , wherein the anti-psychotic drugs other than aripiprazole are selected from the group consisting of: risperidone, paliperidone, quetiapine, olanzapine, and metabolites thereof.
12. The method of claim 1 ,
wherein:
the immunogenic carrier of the conjugate is linked to the substituent at the R 1 position of the compound of Formula I via a thiol group;
R 1 is
R 2 is H;
R 3 is H; and
m is 1.
13. The method of claim 2 ,
wherein:
the immunogenic carrier of the conjugate is linked to the substituent at the R 1 position of the compound of Formula I via a thiol group;
R 1 is
R 2 is H;
R 3 is H; and
m is 1.
14. The method of claim 1 , wherein the immunogenic carrier is a protein and wherein the conjugate of the compound of Formula I and the immunogenic carrier has the following structure:
15. The method of claim 2 , wherein the immunogenic carrier is a protein and wherein the conjugate of the compound of Formula I and the immunogenic carrier has the following structure: