Tricyclic antidepressant drug immunogens, antibodies, labeled conjugates, and related derivatives

• US 4,495,281 A
• Filed: 10/21/1982
• Issued: 01/22/1985
• Est. Priority Date: 10/21/1982
• Status: Expired due to Fees

• Current Assignee: Miles Laboratories, Inc. (Bayer AG)
• Original Assignee: Miles Laboratories, Inc. (Bayer AG)
• Inventors: Buckler, Robert T., Ward, Frederick E.
• Primary Examiner(s): SCHAIN, HOWARD
• Application Number:
  US06/435,633
• Time in Patent Office: 824 Days
• Field of Search: 260/112 R, 260/112 B, 260/121, 424/85, 424/88, 435/7, 435/188, 436/528, 436/536
• US Class Current: 436/537
• CPC Class Codes: C07D 223/22 Dibenz [b, f] azepines; Hydrogenated dibenz [b, f] azepines
• CPC Class Codes: C07D 303/14 by free hydroxyl radicals
• CPC Class Codes: C07D 405/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07H 17/075 Benzo[b]pyran-2-ones
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: G01N 33/532 Production of labelled immunochemicals
• CPC Class Codes: G01N 33/9466 Antidepressants
• CPC Class Codes: Y10S 435/961 including a step of forming, releasing, or exposing the antigen or forming the hapten-immunogenic carrier complex or the antigen per se
• CPC Class Codes: Y10S 435/975 Kit
• CPC Class Codes: Y10S 436/815 Test for named compound or class of compounds
• CPC Class Codes: Y10S 530/806 Antigenic peptides or proteins

Abstract

Tricyclic antidepressant drug (e.g., imipramine, desipramine, amitriptyline, or nortriptyline) immunogens, antibodies prepared therefrom, labeled conjugates, synthetic intermediates, and the use of such antibodies and labeled conjugates in immunoassays for determining such drug. The immunogens comprise the drug coupled at its 2'"'"'-position to an immunogenic carrier material. Similarly, the labeled conjugates and synthetic intermediates are 2'"'"'-derivatives of the drug or a precursor thereof. The antibodies and labeled reagents are particularly useful in certain homogeneous nonradioisotopic immunoassays for measuring tricyclic antidepressant drugs in biological fluids such as serum.

Claims

1. A tricyclic antidepressant drug immunogen of the formula:

##STR12## wherein Aryl represents a tricyclic antidepressant drug nucleus selected from the group consisting of ##STR13## wherein W is hydrogen or methyl;

R is a bond or a linking group;

Carrier is an immunogenic carrier material; and

p is on the average from 1 to about 50.

2. The immunogen of claim 1 wherein said linking group is a chain comprising between 1 and 20 atoms, excluding hydrogen.

3. The immunogen of claim 2 wherein said chain is aliphatic.

4. The immunogen of claim 1 wherein said carrier material is a protein or polypeptide.

5. The immunogen of claim 4 wherein R is a bond forming an amide couple to carboxyl groups in said carrier.

6. The immunogen of claim 5 wherein said carrier material is an albumin.

15. An antibody prepared against the immunogen of claim 1.

18. In an immunoassay method for determining a tricyclic antipressant drug,

the improvement which comprises employing an antibody of claim 15 as the antibody to the tricyclic antidepressant drug.

19. In reagent means for determining a tricyclic antidepressant drug by immunoassay,

the improvement which comprises employing an antibody of claim 15 as the antibody to the tricyclic antidepressant drug.

20. A test kit for determining a tricyclic antidepressant drug by homogeneous immunoassay, comprising (a) an antibody of claim 15 and (b) a labeled conjugate of the drug under assay which has a detectable property which is altered when bound with said antibody.

21. A test device for determining a tricyclic antidepressant drug by homogeneous immunoassay, comprising (a) a reagent composition including an antibody of claim 15 and a labeled conjugate of the drug under assay which has a detectable property which is altered when bound with said antibody, and (b) a solid carrier member incorporated with said reagent composition.

7. An imipramine or desipramine immunogen of the formula:

##STR14## wherein W is hydrogen or methyl, R is a bond or a linking group, Carrier is an immunogenic carrier material, and p is on the average from 1 to about 50.

8. The immunogen of claim 7 wherein said linking group is a chain comprising between 1 and 20 atoms, excluding hydrogen.

9. The immunogen of claim 7 wherein said carrier material is a protein or polypeptide and R is a bond forming an amide couple to carboxyl groups in said carrier.

10. The immunogen of claim 9 wherein said carrier material is an albumin.

16. An antibody prepared against the immunogen of claim 7.

11. An amitriptyline or nortriptyline immunogen of the formula:

##STR15## wherein W is hydrogen or methyl, R is a bond or a linking group, Carrier is an immunogenic carrier material, and p is on the average from 1 to about 50.

12. The immunogen of claim 11 wherein said linking group is a chain comprising between 1 and 20 atoms, excluding hydrogen.

13. The immunogen of claim 11 wherein said carrier material is a protein or polypeptide and R is a bond forming an amide couple to carboxyl groups in said carrier.

14. The immunogen of claim 13 wherein said carrier material is an albumin.

17. An antibody prepared against the immunogen of claim 11.