ABSTRACT
A chemical investigation of the sponge Verongula cf. rigida led to the isolation of 13 merosesquiterpenes, among which quintaquinone (2), 5-epi-nakijiquinone L (3), and 3-farnesyl-2-hydroxy-5-methoxyquinone (4) were isolated and reported here for the first time. Particularly, compound 2 is the first member of merosesquiterpenes with a polyketide side chain substituted on C-19. All of the isolated compounds were examined for steroid 5α-reductase inhibitory activity. Cyclospongiaquinone 1 (5) showed a strong activity in the same range as that of standard finasteride.
Subject(s)
5-alpha Reductase Inhibitors/pharmacology , Finasteride/pharmacology , Sesquiterpenes/isolation & purification , 5-alpha Reductase Inhibitors/chemistry , 5-alpha Reductase Inhibitors/isolation & purification , Animals , Finasteride/chemistry , Finasteride/isolation & purification , Humans , Male , Molecular Structure , Porifera/chemistry , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacologyABSTRACT
Novel sample preparation approaches for HPLC bioanalysis based on the phenomenon that acetonitrile can be separated from water by adding salts or cooling at subzero temperatures have been reported. These two methods are superior to conventional liquid-liquid extraction since the separated acetonitrile phase can be directly injected to the RP-LC system. However, the salting-out method suffers from a potential problem that the remained salt in the acetonitrile phase may harm the MS detector, while the subzero-temperature method is troublesome to operate. Here, we have reported a similar phase separation phenomenon that the acetonitrile aqueous mixture can be separated by adding a hydrophobic solvent; and capitalising on this phase transition phenomenon, we have proposed an alternative approach, named solvent induced phase transition extraction (SIPTE), to extract drug from plasma for HPLC-MS analysis. The proposed SIPTE method is much simpler and avoids contaminating the MS detector. Three structurally diverse drugs were selected as test compounds to design the SIPTE method and to validate the efficiency of this method. The four goals of plasma sample pretreatment for HPLC-MS analysis, i.e. removal of proteins, removal of other low-molecular interferences, preconcentration of the analytes of interest, and matching the sample solvent with the HPLC-MS system, can be rapidly performed in a very simple step by using the SIPTE method.
Subject(s)
Acetonitriles/chemistry , Chemical Fractionation/methods , Chromatography, High Pressure Liquid/methods , Mass Spectrometry/methods , Pharmaceutical Preparations/blood , Chloroform/chemistry , Diterpenes/blood , Diterpenes/isolation & purification , Finasteride/blood , Finasteride/isolation & purification , Humans , Hydrophobic and Hydrophilic Interactions , Models, Molecular , Pharmaceutical Preparations/isolation & purification , Piperazines/blood , Piperazines/isolation & purification , Purines/blood , Purines/isolation & purification , Reproducibility of Results , Sensitivity and Specificity , Sildenafil Citrate , Sulfones/blood , Sulfones/isolation & purificationABSTRACT
To study the effects of allopregnanolone (AP) depletion on stress-induced dopamine changes in cortical dopamine, the 5alpha-reductase inhibitor finasteride on a gram-scale is required. Two procedures for the extraction of finasteride from tablets are outlined (method A and B). In method A, a suspension of powdered tablets was preliminary extracted with chloroform and the extracts dried and evaporated. The resulting residue was then purified on column chromatography. Method B involves a direct chromatographic separation of the powdered tablets. In terms of isolated yields, the second procedure works well, is cheaper, and less time-consuming. The efficiency of the method was tested by measuring progesterone, AP and THDOC content in plasma and cerebral cortex of rats. The protocol enables the prompt availability of sufficient amount of finasteride in experimental grade, useful in examining the role of endogenous cerebrocortical AP in brain homeostasis.
Subject(s)
5-alpha Reductase Inhibitors , Chemistry, Pharmaceutical/methods , Chromatography/methods , Enzyme Inhibitors/isolation & purification , Finasteride/isolation & purification , Pregnanolone/antagonists & inhibitors , Animals , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Cerebral Cortex/physiopathology , Chemistry, Pharmaceutical/instrumentation , Chromatography/instrumentation , Desoxycorticosterone/analogs & derivatives , Desoxycorticosterone/antagonists & inhibitors , Desoxycorticosterone/metabolism , Dopamine/metabolism , Enzyme Inhibitors/pharmacology , Finasteride/pharmacology , Pregnanolone/biosynthesis , Pregnanolone/blood , Progesterone/metabolism , Rats , Receptors, GABA-A/metabolism , Stress, Physiological/blood , Stress, Physiological/physiopathology , Time FactorsABSTRACT
This review is focused on the different chromatographic strategies for determination of finasteride and its analogues in biological fluids. These compounds are used for the treatment of benign prostatic hyperplasia. Particular attention is paid to high-performance liquid chromatography with spectrophotometric and mass spectrometric detection, the clean-up procedures are also included. The relationships between pharmacokinetics of finasteride, dose administered and required limit of quantitation of the chromatographic assays are discussed. Tandem mass spectrometry is recommended as the detection method for measuring concentrations <1 ng/ml, while cheaper spectrophotometric detection may be selected for determination of higher concentrations.
