Water-soluble derivatives of lipophilic drugs
AssigneeRoche Diagnostics Operations, Inc.
InventorsMin Li, Robert S. Wu, Jane S.C. Tsai
Life of this patent
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Abstract
A water-soluble reference standard is useful for immunoassays of a lipophilic drugs. The reference standard is a compound of formula (I): G-(L)n—Y (I); where G is a lipophilic drug; L is a linker which is an alkyl group or heteroalkyl group containing from 1 to 20 carbon atoms; n is 0 or 1; and Y is a water-solubilizing group such as —SO3−, —NR—SO3−, —P(═O)(OH)(O−), or —O—P(═O)(OH)(O−); where R is H or an alkyl group of 1 to 10 carbon atoms.
Claims44
A water-soluble reference standard for an immunoassay of a lipophilic drug, of formula (I):
- G-(L)n—Y (I);
- wherein
- G is a lipophilic drug;
- L is a linker selected from the group consisting of alkyl and heteroalkyl containing from 1 to 20 carbon atoms;
- n is 0 or 1;
- and
- Y is a water-solubilizing group selected from the group consisting of —SO3−, —NR—SO3−, —P(═O)(OH)(O−), or —O—P(═O)(OH)(O−);
- wherein R is selected from the group consisting of H and an alkyl group comprising 1 to 10 carbon atoms.
A water-soluble reference standard for an immunoassay of benzodiazepines, of formula (II):
- 14
- wherein X1, X2, X3 and X4 are independently selected from the group consisting of hydrogen, F, Cl, Br, nitro, amino, and alkylamido;
- E is selected from the group consisting of —H, alkyl, —OH, —COOH, and —COOR′, where R′ is an alkyl group containing from 1 to 10 carbon atoms;
- A is an aryl group
- L is a linker group selected from the group consisting of alkyl and heteroalkyl containing from 1-20 carbon atoms;
- n is 0 or 1;and
- Y is selected from the group consisting of —SO3−, —NR′—SO3−, —P(═O)(OH)(O−), or —O—P(═O)(OH)(O−);
- wherein R′ is selected from the group consisting of H and an alkyl group comprising 1 to 10 carbon atoms;
- wherein the compound has a solubility of at least 100 micrograms per milliliter in water at 25° C.
A water-soluble reference standard for an immunoassay of THC, of formula (V):
- 15
- wherein L is a selected from the group consisting of alkyl and heteroalkyl containing from 1 to 20 carbon atoms;
- n is 0 or 1;
- and
- Y is selected from the group consisting of —SO3−, —NR′—SO3−, —P(═O)(OH)(O−), or —O—P(═O)(OH)(O−);
- wherein R′ is selected from the group consisting of H and an alkyl group comprising 1 to 10 carbon atoms;
- and
- wherein the compound has a solubility of at least 100 micrograms per milliliter in water at 25° C.
A method of forming a water-soluble reference standard for immunoassay of a lipophilic drug, comprising:
- functionalizing a lipophilic drug with a water-solubilizing group selected from the group consisting of —SO3−, —NR′—SO3−, —P(═O)(OH)(O−), or —O—P(═O)(OH)(O−).
A method of forming a water soluble reference standard for an immunoassay of THC, comprising:
- reacting THC-9-carboxylic acid with DPPA and sodium hydroxide to form THC-9-amine;
- and
- treating THC-9-amine with chlorosulfonic acid.
A method of forming a water soluble reference standard for an immunoassay of THC, comprising:
- treating THC-9-carboxylic acid with DCC and NHS to form an ester;
- treating the ester with ammonium hydroxide to form THC-9-amide;
- reducing the THC-9-amide with lithium aluminum hydride to form THC-9-amine;
- and
- reacting the THC-9-amine with chlorosulfonic acid.
A method of forming water soluble reference standard for an immunoassay of benzodiazepines, comprising:
- treating didesethylflurazepam with chlorosulfonic acid.
Dependencies are inferred from the claim text.