AIMTo study the impurity in the drug megestrol acetate.

METHODSChromatography methods were used to separate the chemical constituents. Their structures were determined by NMR and MS spectral analysis.

RESULTSTwo new epimers were isolated from the mother liquid of the drug megestrol acetate.

CONCLUSIONThese new epimers were identified as 17alpha-acetoxy-2beta,6alpha-dimethylprega-4-ene-3,20-dione (1) and 17alpha-acetoxy-2alpha,6alpha-dimethylprega-4-ene-3,20-dione (2).

Drug Contamination ; Megestrol Acetate ; chemical synthesis ; chemistry ; Molecular Conformation ; Molecular Structure ; Pregnanediones ; chemistry ; isolation & purification ; Stereoisomerism

Althesin(CT 1341), a new steroid anesthetic, was tried clinically as an induction agent. All 24 patients were in the physical status class 1 by A.S.A. classification. Dosage of althesin given intravenously was 50ul/kg B.W. and the injection speed for the given dose was 15 seconds. The following results were obtained. 1) Induction time was 42+/-19. 7 seconds. 2) No significant changes in pulse rate were found after intravenous injection of althesin. 3) Systolic blood pressure was decreased 8mmHg (p<0.01) after one minute of injection and 11 mmHg (p<0.01) after three minutes and raised to preanesthetic level after five minutes. No significant change was found in diastolic blood pressure. 4) Respiratory rate was increased 3/min. (p<0.05) after three minutes. 5) Minute volume was decreased 170Gml (p<0.01) after one minute and 700ml (p<0.05> after three minutes. 6) As complications, involuntary muscle movement of extremities was observed in two cases and transient apnea in one case.
Alfaxalone Alfadolone Mixture* ; Apnea ; Blood Pressure ; Classification ; Extremities ; Heart Rate ; Humans ; Injections, Intravenous ; Muscle, Smooth ; Respiratory Rate

OBJECTIVE: To identify 1) whether the endogenous steroid hormone metabolism in patients with pelvic organ prolapse was different from that of normal women, 2) the relationship between endogenous steroid hormone metabolites and the stage of the pelvic organ prolapse. METHODS: Twenty postmenopausal women who were clinically diagnosed as having pelvic organ prolapse and 20 volunteer postmenopausal women not having pelvic organ prolapse were included in the study. We compared the urinary profiles of endogenous steroids between the two groups and investigated the relationship between urinary profiles of the endogenous steroids and the degree of pelvic organ prolapse. Urinary profiles of the endogenous steroids were assayed by gas chromatography-mass spectrometry. RESULTS: The ages of the patients and control group were 64.6 +/- 6.5 and 63.5 +/- 3.9 years, and the Body Mass Index (BMI) was 23.96 +/- 3.14 and 24.11 +/- 2.73 kg/m2 in patients and in normal subjects, respectively. The number of patients in each stage were 4 in stage I, 4 in stage II, 6 in stage III and 6 in stage IV. 5-androstene-3beta, 16beta, 17beta-triol (5-AT), 11beta-hydroxy androstenedione (An) and 17beta-estradiol were significantly increased in patients with pelvic organ prolapse over that of the control group (0.76 +/- 0.67 vs 0.06 +/- 0.03 micro mole/g creatinine; p=0.002, 1.16 +/- 0.83 vs 0.65 +/- 0.23 micro mole/g creatinine; p=0.04, 15.08 +/- 9.81 vs 8.53 +/- 6.19 micro mole/g creatinine; p=0.04). However, tetrahydrocortisone (THE) was significantly increased in the control group over that in patients having pelvic organ prolapse (9.80 +/- 6.21 vs 5.22 +/- 4.89 micro mole/g creatinine; p=0.04). The androgen metabolites, 5-AT and THE significantly correlated with the POP-Q stage (R=0.418; p=0.027, R=0.46; p=0.016). Among the estrogen metabolites, 17beta-estradiol was correlated to the POP-Q stage but not mathematically significantly (R=0.38; p=0.05) and the 17beta-estradiol/estrone ratio weakly correlated to pelvic organ prolapse stage (R=0.14; p=0.49), by showing a low correlation coefficiency. CONCLUSION: The urinary concentrations of 17beta-estradiol, 5-AT and 11beta-hydroxy An increased in patients with pelvic organ prolapse over that of the control group and 5-AT, THE and 17beta-estradiol showed a relationship to the progression of pelvic organ prolapse in Korean women. The metabolites of endogenous steroid hormones could be contributing factors in the pathogenesis of pelvic organ prolapse.
Androstenedione ; Body Mass Index ; Creatinine ; Estrogens ; Female ; Gas Chromatography-Mass Spectrometry ; Humans ; Metabolism* ; Pelvic Organ Prolapse* ; Steroids ; Tetrahydrocortisone ; Volunteers

OBJECTIVETo study the association between phthalate esters (PAEs) metabolites in maternal urine and 11beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2 ) enzyme activity, explore the possible mechanism of PAEs effect on fetal development.

METHODSAll of 33 cases of intrauterine growth retardation (IUGR) newborn were selected by random sampling in 2012. And 33 cases of normal control newborn were enrolled, use high performance liquid chromatography-tandem mass spectrometry method was used to detect 4 kinds of phthalate esters (PAEs) metabolites in maternal urine: mono-n-butyl phthalate ester (MBP), mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) and three kinds of cortisol corticosterone metabolites, tetrahydrocortisol (THF), allo-tetrahydrocortisol (allo-THF), tetrahydrocortisone (THE), and analyze the association between phthalate esters (PAEs) metabolites in maternal urine and 11β-HSD2 enzyme activity.

RESULTSMBP, MEHP, MEHHP, MEOHP metabolites can be detected in 98% (65 cases) , 89% (59 cases), 91% (60 cases), 91% (60 cases) of all 66 maternal urine samples, respectively. The median concentrations of test material in case group were 31.20 ng/ml for MBP, 24.61 ng/ml for MEHHP, 11.72 ng/ml for MEOHP and 48.67 ng/ml for SumDEHP which were significantly higher than those of the control group (were 17.32, 12.03, 5.68 and 28.64 ng/ml); 11β-HSD2 activity in case group ((THF+allo-THF)/THE = (0.79 ± 0.09) ng/ml) was significantly lower than that of the control group((THF+allo-THF)/THE = (0.58 ± 0.04) ng/ml); PAEs metabolites MBP (β' = 1.12), MEHHP(β' = 1.14), MEOHP(β' = 1.10), SumDEHP(β' = 1.08) in baby boy mother's urine was reversely correlated to 11β-HSD2 activity.

CONCLUSIONSPAEs could affect fetal development by inhibit 11β-HSD2 activity.

11-beta-Hydroxysteroid Dehydrogenase Type 2 ; Chromatography, Liquid ; Diethylhexyl Phthalate ; analogs & derivatives ; Fetal Development ; Humans ; Infant, Newborn ; Male ; Mass Spectrometry ; Phthalic Acids ; Tetrahydrocortisol ; analogs & derivatives ; Tetrahydrocortisone