Immunoassays with novel labeled carbamazepine hapten analogues
First Claim
1. An immunoassay method for carbamazepine comprising:
- A. contacting a liquid sample, containing carbamazepine, with a labeled carbamazepine analogue in the presence of antibodies for carbamazepine under conditions that promote the formation of carbamazepine/antibody immunocomplexes; and
B. determining the quantity of the drug in the liquid by measuring bound or unbound labeled drug analogue;
wherein the labeled carbamazepine analogue 1 has the structure (I);
##STR12## R represents hydrogen or lower alkyl of 1 to 6 carbon atoms R1 is alkylene of 1 to 3 carbon atoms sufficient to form a heterocyclic group selected from 1,4-piperazinylene;
2,5-dimethyl-1,4-piperazinylene;
1,3-imidazolidinylene, and 1,4-hexahydrodiazepinylene;
R2, R3, R4, and R5 each independently represent alkylene groups of 2 to 10 carbon atoms, or phenylene;
R7 is hydrogen or methyl;
each Z independently represents --O--, --S--, or --NR-- wherein R represents hydrogen or lower alkyl of 1 to 6 carbon atoms;
LABEL is an enzyme;
1is 0, 1 or 2;
m is 1 or 2;
n is 0, 1, or 2; and
(i) the sum of carbon and hetero atoms in the linking chain, comprising the atoms included in R2, R3, R4, and R5, excluding the amide group of carbamazepine and the carbonyl group joining the label to the linking chain, is 5 to 40, (ii) provided that the bracketed components 1, m and n of structure I can appear therein in any order, and (iii) only one R2, R3, R4, or R5 group can be phenylene.
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Abstract
An immunoassay method and analytical elements for detecting carbamazepine drugs, for example, in body fluids, is described. The immunoassay method comprises:
(A) contacting a liquid sample, containing carbamazepine, with a labeled carbamazepine analogue in the presence of antibodies for carbamazepine under conditions that promote the formation of carbamazepine/antibody immunocomplexes; and
(B) determining the quantity of the drug in the liquid by measuring bound or unbound labeled drug analogue; characterized in that the labeled carbamazepine comprises:
(1) a label, of the type used in immunoassays, having an amine or sulfhydryl group;
(2) a carbamazepine nucleus; and
(3) a linking chain linking the carboxamide group of the carbamazepine nucleus to the label, said linking chain having about 4 to about 40 atoms consisting of:
(a) alkylene groups; and
(b) heterocyclic ring groups, each group being joined into the linking group through chemical groups selected from
(a) esters,
(b) amides,
(c) heteroatoms selected from --O--, --S--, and --NR--; wherein each R independently represents hydrogen or C1 to C6 alkyl; and
(d) carbonyl groups.
The elements of the invention are preferably dry, thin film analytical elements comprising a labeled carbamazepine analogue as described.
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Citations
13 Claims
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1. An immunoassay method for carbamazepine comprising:
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A. contacting a liquid sample, containing carbamazepine, with a labeled carbamazepine analogue in the presence of antibodies for carbamazepine under conditions that promote the formation of carbamazepine/antibody immunocomplexes; and B. determining the quantity of the drug in the liquid by measuring bound or unbound labeled drug analogue;
wherein the labeled carbamazepine analogue 1 has the structure (I);
##STR12## R represents hydrogen or lower alkyl of 1 to 6 carbon atoms R1 is alkylene of 1 to 3 carbon atoms sufficient to form a heterocyclic group selected from 1,4-piperazinylene;
2,5-dimethyl-1,4-piperazinylene;
1,3-imidazolidinylene, and 1,4-hexahydrodiazepinylene;R2, R3, R4, and R5 each independently represent alkylene groups of 2 to 10 carbon atoms, or phenylene; R7 is hydrogen or methyl; each Z independently represents --O--, --S--, or --NR-- wherein R represents hydrogen or lower alkyl of 1 to 6 carbon atoms; LABEL is an enzyme; 1is 0, 1 or 2; m is 1 or 2; n is 0, 1, or 2; and (i) the sum of carbon and hetero atoms in the linking chain, comprising the atoms included in R2, R3, R4, and R5, excluding the amide group of carbamazepine and the carbonyl group joining the label to the linking chain, is 5 to 40, (ii) provided that the bracketed components 1, m and n of structure I can appear therein in any order, and (iii) only one R2, R3, R4, or R5 group can be phenylene. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13)
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10. An immunoassay method for carbamazepine, comprising the steps:
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A. contacting a liquid sample, containing carbamazepine, with a labeled carbamazepine analogue in the presence of antibodies for carbamazepine under conditions that promote the formation of carbamazepine antibody immuno complexes; B. applying a developing liquid to separate complexed labeled carbamazepine from uncomplexed labeled carbamazepine; and C. determining the quantity of the drug in the liquid by measuring bound or unbound labeled drug analogue;
wherein the labeled carbamazepine analogue labeled carbamazepine analogue is a conjugate of amine enriched horseradish peroxidase and a member selected from the group consisting of N-[6-(4Succinimidoxycarbonylbutyramido)hexyl]-carbamazepine; and
N-{4-[3-(4-Succinimidoxycarbonylbutyramido)propylaminocarbonyl]butyl}carbamazepine.
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Specification