ABSTRACT
Regression equation modelling was used for the correlation of gas chromatographic relative retention times tRR of anabolic steroids, stimulants and narcotics with their molecular characteristics in order to create a model for the prediction of tRR values of unanalyzed molecules. Predicting chromatographic retention parameters is one of the main goals of the quantitative structure-retention relationships (QSRR) methodology. To be performed, QSRR studies require two tools; a methodology for the extraction of the structural characteristics and a statistical program for the correlation of these characteristics with the chromatographic data.
Subject(s)
Chromatography, Gas , Doping in Sports , Illicit Drugs/chemistry , Substance Abuse Detection , Anabolic Agents/chemistry , Central Nervous System Stimulants/chemistry , Doping in Sports/prevention & control , Models, Chemical , Models, Statistical , Narcotics/chemistry , Regression Analysis , Software , Structure-Activity RelationshipABSTRACT
The ADAPT software system was used to create models for the prediction of gas chromatographic relative retention times (RRTs) of stimulants and narcotics that are analyzed in doping control of athletes. The two main methods that were followed for building the models were the quantitative structure-retention relationship (QSRR) and multiple linear regression analysis. The main proposed model for the entire data set had a multiple correlation coefficient R = 0.991 and standard error s = 0.046 or approximately 4.5%. Because of the relatively high standard error of the main model, a second model was built on a subset of compounds with R = 0.982 and s = 0.027 or approximately 2.5%.
Subject(s)
Central Nervous System Stimulants/analysis , Narcotics/analysis , Central Nervous System Stimulants/chemistry , Chromatography, Gas , Narcotics/chemistry , Predictive Value of Tests , Regression Analysis , SoftwareABSTRACT
The prediction of gas chromatographic relative retention times (RRTs) of anabolic steroids, used in the doping control of athletes, was performed by a quantitative structure-retention relationship (QSRR) and multiple linear regression analysis study. A nine-variable model was generated with a multiple correlation coefficient R = 0.991 and relative standard error of less than 3%. Preliminary results indicated that the application of the model, especially in the prediction of RRTs of metabolites of the anabolic steroids, will be helpful.
Subject(s)
Anabolic Agents/analysis , Gas Chromatography-Mass Spectrometry , Predictive Value of Tests , Regression AnalysisSubject(s)
Cryptorchidism/surgery , Testis/metabolism , Testosterone/blood , Child , Chorionic Gonadotropin/pharmacology , Humans , Male , Postoperative PeriodABSTRACT
The catatonic activity, prolongation of phenobarbital sleeping-time, convulsant action and disruption of nest-building activity was assessed in mice subjected to 4 cannabis pyrolysis products and their tobacco analogues. All but one of the cannabis fractions prolonged the pentobarbital sleeping-time and disrupted the nest-building activity of mice in a way not related to their content in the main cannabinoids. Nest-building activity seems to be the most valid assay we have used so far.
Subject(s)
Behavior, Animal/drug effects , Cannabinoids/pharmacology , Animals , Anticonvulsants , Cannabinoids/isolation & purification , Hot Temperature , Male , Mice , Nesting Behavior/drug effects , Plants, Toxic , Sleep/drug effects , Smoke , NicotianaABSTRACT
The antitumour agent chlorambucil (4[4-bis(2-chloroethyl)aminophenyl]-butyric acid) is converted by beta-oxidation in vivo into phenylacetic mustard (2[4-bis(2-chloroethyl)aminophenyl]acetic acid). This process may be disadvantageous from a therapeutic viewpoint since the metabolite has half the therapeutic index of the parent drug against the Walker 256 carcinoma in rats. In seeking to retard beta-oxidation, selectively deuterated analogues have been synthesised and administered to rats. Plasma levels of phenylacetic mustard after giving chlorambucil-beta-d2 were lower than those given by unlabelled drug, but the therapeutic activity was not significantly altered by deuteration. A dehydro derivative of chlorambucil was detected as an intermediate in the beta-oxidation pathway. The isotopic compositions of this metabolite, and of recovered chlorambucil, were measured in plasma samples taken after giving labelled chlorambucil (alpha-d2 and beta-d2 variants) to rats. Deuterium was almost totally lost from the alpha-d2 form and from its metabolite after 30 min and partially lost in 10 min. The beta-d2 variant and its dehydro-derivative retained the label. Possible mechanisms for deuteration loss are discussed. The design of novel analogues, based on these metabolic studies, is proposed.
