ABSTRACT
The syntheses of stable isotope labelled internal standards of important CYP-isoform selective probes, like testosterone 1, diclofenac 3, midazolam 5, and dextromethorphan 7, as well as their corresponding hydroxylated metabolites 6ß-hydroxytestosterone 2, 4'-hydroxydiclofenac 4, 1'-hydroxymidazolam 6 and dextrorphan 8 are reported. Microwave-enhanced H/D-exchange reactions applying either acid, base, or homogeneous and heterogeneous transition metal catalysis, or combinations thereof proved to be highly efficient for direct deuterium labelling of the above mentioned probes. Compared to conventional stepwise synthetic approaches, the combination of H/D exchange and biotransformation provides the potential for considerable time- and cost savings, in particular for the synthesis of the stable isotope labelled internal standards of 4'-hydroxydiclofenac 4 and 1'-hydroxymidazolam 6.
Subject(s)
Diclofenac/analogs & derivatives , Isotope Labeling/methods , Midazolam/analogs & derivatives , Pharmaceutical Preparations/chemistry , Cytochrome P-450 Enzyme System/metabolism , Deuterium Exchange Measurement , Diclofenac/chemical synthesis , Diclofenac/chemistry , Diclofenac/metabolism , Microwaves , Midazolam/chemical synthesis , Midazolam/chemistry , Midazolam/metabolism , Molecular Structure , Pharmaceutical Preparations/metabolism , Reference StandardsABSTRACT
Up to now a rare affection difficult to diagnose in its abdominal localizations, actinomycosis is becoming of topical interest because of the appearance of a new form of the disease: utero-ovarian infection associated with an intra-uterine contraceptive device (IUD). A recent case, of surgical expression, is reported and used as a basis for an update of epidemiologic and pathogenic data concerning the affection. Diagnosis should be facilitated by regular cytobacteriologic examinations in women with the IUD, and simple preventive measures should limit the number of severe forms sometimes requiring more or less extensive excision.
