ABSTRACT
OBJECTIVE: To investigate the thermostability of four crystal forms of fluconazole. METHODS: The thermostability of fluconazole was analyzed using XRD, DSC and TGA, and the structural characteristics of the crystal forms and crystalline transformation were determined using XRD with in-situ high temperature accessories. RESULTS: The crystal form I and II had good at thermostability, and the crystal structure of form III changed at about 40°C. The monohydrate transformed to form II at about 70°. CONCLUSION: The different crystal forms of fluconazole have distinct thermostability. The result of this study would provide a comprehensive reference for the quality evaluation of fluconazole.
ABSTRACT
OBJECTIVE: To establish an HPLC gradient elution method for the determination of related substances in fluconazole bulk drug. METHODS: The separation was achieved by using an ODS column with gradient elution of mobile phase composed of 0.01 mol · L-1 ammonium formate and acetonitrile. The flow rate was 0.5 mL · min-1. The UV detection wavelength was 261 nm, injection volume is 20 μL. RESULTS: Fluconazole and its related substances can be separated effectively by this method, linear relation of fluconazole and impurity B-D were good, the detection limit were 0.20, 0.0052, 0.0073, 0.13 μg · mL-1, seventeen batches sample from nine manufacturers were determined. The related substances in fluconazole bulk drug were effectively determined. CONCLUSION: The HPLC method is rapid and accurate which may be used for the inspection of related substances in fluconazole bulk drug. Copyright 2012 by the Chinese Pharmaceutical Association.
ABSTRACT
<p><b>UNLABELLED</b>The present study was aimed to study the effect of hydrogen sulfide (H(2)S) on rat myocardial ischemia/reperfusion (I/R) injury and whether the effect is mediated by c-Fos protein expression. Male Sprague-Dawley rats were randomly divided into 4 groups:</p><p><b>CONTROL GROUP</b>sham treatment; I/R group: the rat anterior descending branch of left coronary artery was occluded for 30 min and then released to allow reperfusion for 60 min; NaHS (exogenous H(2)S donor) groups: the rats were pretreated with NaHS at 2.8 μmol/kg body weight and 14 μmol/kg body weight (i.v.), respectively, before I/R treatment. Hemodynamics (LVSP, LV±dp/dt(max)) and electrocardiogram (ECG, lead II) were monitored continuously with multi-channel physiological signal analysis system after reperfusion. Myocardial infarct size was measured using triphenyltetrazolium chloride (TTC) staining. H(2)S concentration in the plasma was determined with a spectrophotometer. Morphological and ultrastructural changes in myocardial tissue were evaluated by HE staining and by a transmission electron microscope. The evaluation of c-Fos protein expression in myocardial tissue was performed by immunohistological staining. The results showed that H(2)S concentration in rat plasma in I/R group was significantly decreased compared with that in the control group [(30.32±5.26) vs (58.28±7.86) μmol/L, P<0.05]. NaHS at 2.8 and 14 μmol/kg body weight reduced the changes in LVSP, LV±dp/dt(max) in rat myocardium induced by I/R injury. The values of LVSP, +dp/dt(max) and -dp/dt(max) at 60 min during myocardial reperfusion were enhanced from (75.93±1.10)%, (66.27±4.78)% and (66.01±4.79)% in I/R group to (84.34±2.24)%, (76.38±1.93)% and (75.47±5.29)% in 2.8 μmol/kg body weight NaHS group (P<0.05, P<0.01, n=6), (88.40±2.88)%, (80.10±2.09)% and (80.48±6.20)% in 14 μmol/kg body weight NaHS group (P<0.01, n=6), respectively. Compared with that in 2.8 μmol/kg body weight NaHS group, the enhancing effect was more prominent in 14 μmol/kg body weight NaHS group. NaHS at 14 μmol/kg body weight markedly alleviated the injury in morphological changes and decreased c-Fos protein expression in myocardial tissue compared with that in I/R group (0.20±0.06 vs 0.32±0.10, P<0.05). These results suggest that H(2)S protects myocardium against I/R injury and this protective effect may be related to the down-regulation of c-Fos protein expression.</p>
Subject(s)
Animals , Male , Rats , Cardiotonic Agents , Pharmacology , Coronary Vessels , Down-Regulation , Hemodynamics , Hydrogen Sulfide , Pharmacology , Myocardial Infarction , Pathology , Myocardial Reperfusion Injury , Drug Therapy , Metabolism , Myocardium , Metabolism , Proto-Oncogene Proteins c-fos , Metabolism , Rats, Sprague-Dawley , Sulfides , PharmacologyABSTRACT
This study was purposed to investigate the relationship of expressions of gluthatione-S-transferase-pi (GST-pi), multidrug resistance protein-1 (MRP-1), lung resistance protein (LRP) with multidrug resistance of acute leukemia (AL), the correlation between 3 kinds protein expressions and the correlation of their protein expression with clinical features of AL patients. The S-P immunohistochemical staining method was used to determine the expressions of GST-pi, MRP1 and LRP proteins in 80 AL patients and 30 normal subjects. The results showed that there was the correlation between GST-pi, MRP1, LRP protein expression and chemotherapy resistance, meanwhile CR rates of patients with positive expression of those proteins were lower than that of patients with negative expression (P<0.05), so those protein expressions may be accounted for poor prognosis. There was the positive relationship between expression of GST-pi and MRP1 in refractory group (r=0.851, P<0.01). It is concluded that co-examination of GST-pi and MRP1 has greater significance than examination of one kind of protein in evaluating poor prognosis of leukemia patients. LRP protein expression increase obviously when WBC counts >or= 10 x 10(9)/L (63.6%, P<0.05), therefore LRP protein has great judging value for evaluating drug resistance and prognosis of acute leukemia patients whose peripheral blood WBC counts were high.