Abstract: Compositions, methods, assays, and kits providing or incorporating derivatives of mitragynine, particularly as haptens and immunogens.

Abstract: Levetiracetam (LEV) derivatives, methods for synthesizing LEV derivatives, and immunodiagnostic assays for LEV. The synthesis methods described herein include chirally-selective, liquid-phase synthesis steps to produce selected LEV derivatives in high-yield. LEV derivatives can include operative groups, such as: immunogenic moieties that can be used to prepare anti-LEV antibodies; antigenic moieties that can be used in immunodiagnostic assays for LEV; or tracer moieties that can be used in immunodiagnostic assays. Additionally, the LEV derivatives can be used in immunodiagnostic assays to compete with LEV for anti-LEV antibodies.

Abstract: The invention teaches derivatives of ascomycin and methods of preparing immunogens and other conjugates useful in immunoassays for quantitatively measuring concentrations of tacrolimus in patient specimens. Antibodies produced from the disclosed immunogens capable of binding to tacrolimus with cross-reactivity of no more than 5% with each of 15-O-demethyl tacrolimus, 31-O-demethyl tacrolimus, and 13,31-O-didemethyl tacrolimus, less than 40% with 13-O-demethyl tacrolimus, and less than 1% with cyclosporin, rapamycin, mycophenolic acid, prednisone, hydrocortisol, and prednisolone are described. Further, immunoassays for measuring the concentration of tacrolimus using such antibodies are taught.

Abstract: The invention teaches derivatives of mycophenolic alcohol and methods of preparing immunogens and other conjugates useful in immunoassays for quantitatively measuring concentrations of mycophenolic acid (MPA) and/or active metabolites of MPA in patient specimens. Antibodies produced from the disclosed immunogens capable of binding to MPA with cross-reactivity of no more than 5% with inactive metabolites and commonly co-prescribed drugs. Further, immunoassays for measuring the concentration of MPA using such antibodies are taught.

Abstract: The present invention provides a system for the improved detection of ecstasy-class compounds in biological samples. New ecstasy-class analogs are provided for detection of such ecstasy-class drugs. These analogs are compounds, or salts thereof, of a 2-amino-methylenedioxyphenyl (MDP) derivative attached to Z, where Z is a moiety capable of bonding, either directly or indirectly, with an immunogenic carrier, a detectable label, or a solid capture vehicle. Such analogs may be used to construct immunogens, enzyme or enzyme-donor conjugates, and other conjugates. The immunogens reproducibly generate antibodies with an exquisite ability to distinguish various ecstasy-class drugs in biological samples from potentially interfering substances. The specific antibodies and the conjugates may be used to distinguish and measure various ecstasy-class compounds in biological samples, such as those obtained from an individual suspected of substance abuse.

Abstract: The present invention provides a system for the improved detection of ecstasy-class compounds in biological samples. New ecstasy-class analogs are provided for detection of such ecstasy-class drugs. These analogs are compounds, or salts thereof, of a 2-amino-methylenedioxyphenyl (MDP) derivative attached to Z, where Z is a moiety capable of bonding, either directly or indirectly, with an immunogenic carrier, a detectable label, or a solid capture vehicle. Such analogs may be used to construct immunogens, enzyme or enzyme-donor conjugates, and other conjugates. The immunogens reproducibly generate antibodies with an exquisite ability to distinguish various ecstasy-class drugs in biological samples from potentially interfering substances. The specific antibodies and the conjugates may be used to distinguish and measure various ecstasy-class compounds in biological samples, such as those obtained from an individual suspected of substance abuse.

Abstract: To detect LSD in biological samples, antibodies are raised to LSD conjugated to a protein carrier, preferably through the indole ring. Selected antibodies are matched with an immunoassay reagent in which the LSD is conjugated in the same position to a labeling or separation means. The set of reagents can be used in immunoassays with remarkably little cross-reactivity with potential interfering substances such a chlorpromazine and ergotamine, and a low false-positive rate in a panel of clinical test samples. Also provided is a set of reagents for measuring glucuronide metabolites of LSD by immunoassay, which permits exposure to LSD to be determined over a longer diagnostic window.

Abstract: The invention relates to an assay system for the improved detection of analytes, and the ability to distinguish them from cross-reacting substances. Samples giving a positive reaction in a direct assay test are treated with a neutralizing antibody that inhibits reactivity of the true analyte, but not the interfering substance. In adsorption type confirmatory assays, the neutralizing antibody is provided in an amount sufficient to adsorb the analyte but not all of the interfering substance. When retested in an immunoassay, the neutralized sample gives a negative result if it originally contained the true analyte. Samples giving a positive reaction in both the direct and confirmatory tests are marked as containing an interfering substance. The confirmatory assay easily distinguishes the true analyte and reduces the rate of false positives, even when the interfering substance is unknown and present at high concentration.

Abstract: Novel chemical analogs are disclosed for the essential heroin metabolite 6-O-acetyl morphine (6MAM). The analogs optionally can be made to contain protein reactive groups, and can be used to form protein conjugates, fluorescently labeled compounds, and solid-phase adsorbants. The proteins conjugates can be used in turn to raise antibodies reactive with 6MAM and having a low cross-reactivity with the closely related opiates, morphine and codeine. The antibodies can be used in combination with labeled analogs in exquisitely sensitive immunoassays suitable for testing for heroin abuse.

Abstract: To improve the detection of LSD in biological samples, antibodies are raised to LSD conjugated to a protein carrier, preferably through the indole ring. Selected antibodies are matched with an immunoassay reagent in which the LSD is conjugated in the same position to a labeling or separation means. The set of reagents can be used in immunoassays with remarkably little cross-reactivity with potential interfering substances such as chlorpromazine and ergotamine, and a low false-positive rate in a panel of clinical test samples. Also provided is a set of reagents for measuring glucuronide metabolites of LSD by immunoassay, which permits exposure to LSD to be determined over a longer diagnostic window.

Abstract: Novel chemical analogs of the methadone metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) are disclosed. The derivatives can be used for formation of EDDP-protein conjugates. The conjugates can be used in turn to raise antibodies reactive with EDDP and having a low cross-reactivity with methadone. The antibodies and EDDP-enzyme polypeptide conjugates provide the basis for specific immunoassays used in monitoring compliance with methadone treatment.

Abstract: This invention relates to improved methods and novel compositions for enzyme complementation assays for qualitative and quantitative determination of a suspected analyte in a sample. The use of enzyme-acceptor and enzyme-donor polypeptides prepared by recombinant DNA techniques, DNA synthesis or chemical polypeptide synthesis techniques which are capable of interacting to form an active enzyme complex having catalytic activity characteristic of .beta.-galactosidase is described. Both homogeneous and heterogeneous assays utilizing these polypeptides are described.

Abstract: This invention relates to improved methods and novel compositions for enzyme complementation assays for qualitative and quantitative determination of a suspected analyte in a sample. The use of enzyme-acceptor and enzyme-donor polypeptides prepared by recombinant DNA techniques, DNA synthesis or chemical polypeptide synthesis techniques which are capable of interacting to form an active enzyme complex having catalytic activity characteristic of .beta.-galactosidase is described. Both homogeneous and heterogeneous assays utilizing these polypeptides are described.

Abstract: Galactopyranoside derivative compounds for use as substrates for hydrolysis by enzymes with .beta.-galactosidase activity are provided. The concentration of the reaction products can be measured by spectroscopy. The compounds find particular use in diagnostic assays for detection of analyte.

Abstract: Compounds are evaluated for their binding to naturally occurring receptors, by employing the natural ligand conjugated to an enzyme donor fragment of .beta.-galactosidase for competing with the sample compound for the natural acceptor binding site or in the absence of competition where the sample compound binds to an allosteric site. By adding the enzyme acceptor fragment of the .beta.-galactosidase and substrate, the binding affinity of the sample compound may be evaluated as a measure of agonist or antagonist capability.

Abstract: The use of omega-acceptor and omega-donor polypeptides (comprising about two-thirds and one-third of the .beta.-galactosidase molecule amino and carboxyl termini, respectively), prepared by recombinant DNA techniques, DNA synthesis, or chemical polypeptide synthesis techniques, which are capable of interacting to form an active enzyme complex having catalytic activity characteristic of .beta.-galactosidase, is described along with improved methods and novel compositions for enzyme complementation assays for qualitative and quantitative determination of a suspected analyte in a sample.

Abstract: The present invention provides an improved assay for measuring thyroxine uptake by thyroxine binding globulin in which thyroxine binding globulin (TBG) activity is measured directly. The method comprises combining a sample in an aqueous solution with an enzyme donor (ED) conjugated to an analogue of polyiodothyronine that competes with thyroxine for thyroxine binding globulin binding sites. An enzyme acceptor (EA) characterized by providing a modulated enzyme activity in relation to the amount of TBG activity is combined with an enzyme donor and sample in an aqueous solution. The amount of enzyme activity in comparison to a control solution having a known amount of available TBG binding sites is determined.

Abstract: A method for detecting the presence of a high-molecular-weight analyte, which uses a variation on complementation assays, comprising (1) providing an enzyme donor (ED)complex comprising ED coupled to an analyte-specific binding molecule, wherein the ED complex retains measurable complementation activity such that active .beta.-galactosidase is formed in the presence of an enzyme acceptor (EA); (2) contacting the ED complex and EA in the presence of a sample suspected of containing a high-molecular-weight analyte that reacts specifically with the analyte-specific binding molecule; and (3) relating the presence of the analyte in the sample to the formation of active .beta.-galactosidase enzyme.

Abstract: The present invention provides reagents for a detectable label for use in specific binding assays. Specifically, modified .beta.-galactosidase enzyme donors (ED) and acceptors (EA) are utilized. Both ED and EA are modified to form separate ED and EA complexes by coupling each with a linking element and a binding moiety which is specific to a binding site in the analyte. The ED and EA complexes are incapable of forming active enzyme in the absence of the analyte. However, when analyte is present, ED and EA complexes which bind to a common analyte in a sample, active .beta.-galactosidase is formed.

Abstract: Novel assays employing enzyme fragments which complex to form an active enzyme are provided. The reagents involved are a member of a specific binding pair bound to a solid surface, a first enzyme fragment conjugated to a member of a specific binding pair complementary or cross-reactive in relation to the analyte or antianalyte and a second enzyme fragment which binds to the conjugate to form an active enzyme, where the first enzyme fragment conjugate may be present in up to substantial excess to ensure at least substantially complete binding of all of the analyte. By distributing the conjugate between the solid surface and the medium in relation to the amount of analyte present, the enzyme activity may be determined in relation to the amount of analyte present, without separating the solid surface and the medium.