Biomedical subjects

C N Carducci

Publications and source records attributed to C N Carducci.

25 records · Page 2Linked to original sources

PubMedDate not supplied

Morphologic changes in livers of hamsters treated with high doses of ursodeoxycholic acid: correlation with bile acids in bile.

The effects of high doses of ursodeoxycholic acid on bile acid composition and the liver morphology was examined in 60 male Syrian golden hamsters. The animals were allocated to five groups: I, control; II and IV received 0.5 g and 1 g of ursodeoxycholic acid per 100 g of standard diet respectively over 30 days and III and V received 0.5 g and 1 g of ursodeoxycholic acid per 100 g of standard diet respectively over 60 days. Bile acids were determined by high performance liquid chromatography. In all treated groups there was a significant increase in chenodeoxycholic and lithocholic acid in the bile. The mean glyco/tauro ratio was significantly higher than in the control group, reaching values > 1 for individual bile acids, except for lithocholic acid values which remained < 1. Under light microscopy, the livers of the hamsters showed damage which was dose/time related, namely portal inflammatory infiltrate, bile duct proliferation, cholestasis, fat infiltration and necrosis. Electron microscopy revealed pronounced changes starting with microvilli edema and extending to canalicular membrane destruction and necrosis. The changes observed in the relation glyco/tauro lithocholic acids, may be due to defence mechanisms to avoid hepatotoxicity. The hepatotoxicity resulting from ursodeoxycholic acid administration is presumed to be due primarily to lithocholic acid or some lithocholic acid metabolite.

Animals↗

PubMedDate not supplied

Determination of related impurities of bile acids in bulk drugs by cyclodextrin-modified micellar electrokinetic chromatography.

A cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) method has been developed and validated for purity determination of two bile acids, ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA). Quantitation of related impurities such as lithocholic acid (LCA), chenodeoxycholic acid (CDCA), cholic acid (CA), and DCA in UDCA and CA in DCA was performed. A running buffer containing 20 mM borate-phosphate, 50 mM sodium dodecyl sulfate (SDS), 2.0 mM beta-cyclodextrin, and acetonitrile was used. Modifiers were added to improve resolution and selectivity. The applied voltage was 25 kV and detection was performed at 185 nm. Validation parameters such as selectivity, linearity, repeatability, intermediate precision, limit of detection, limit of quantitation, and robustness were evaluated. The method was simple and proved to be useful for the purity testing of bile acids in bulk drugs. Good results were obtained for related impurities at concentration levels from 0.05 to 1.5% with respect to the main component, according to international requirements.

Chromatography, Micellar Electrokinetic Capillary↗

PubMedDate not supplied

Determination of inorganic cations by capillary ion electrophoresis in Ilex paraguariensis (St. H.), a plant used to prepare tea in South America.

A practical and economical capillary ion electrophoresis method with indirect UV detection at 214 nm was developed for determination of inorganic cations in plants of Ilex paraguariensis(St. H.) and their infusion known as mate tea, a very popular beverage in South America. A microwave digestion procedure was used to prepare the herbal plants, but the infusion was only diluted. The background electrolyte contained 6mM imidazole and 10mM alpha-hydroxyisobutyric acid, pH 4.0. The running voltage was 20 kV and temperature was 25 degrees C. K, Na, Ca, Mg, and Mn ions were quantitated, and linearity was demonstrated between 0.6 and 120 ppm. The results were in good agreement with those obtained by flame atomic absorption and emission spectrometry. Accuracy of the method was verified by comparison with Beech leaves CRM 100, a standard reference material. The high content of minerals and several oligoelements, especially Mn in mate tea, is considered to be of nutritional interest.

Beverages↗

PubMedDate not supplied

Monitoring the purity of a synthetic peptide by capillary electrophoresis: utilization of an on-line preconcentration method for improved separation and detection sensitivity.

To date, there has been a considerable amount of interest and success in the pharmaceutical industry in the discovery of drug targets and diagnostics utilizing peptides. The success of peptide pharmaceuticals has, however, been accompanied by some failures, both prior to entry and in the clinic. Progress has been made in various areas to improve the effectiveness of the final drug product. One major advance has been in the area of peptide synthesis and control of the purity of the peptide of interest. Recent advances in analytical instrumentation, including advances in capillary electrophoresis, have had a great impact on the ability to separate and detect low quantities of impurities and degradation products during the synthesis of a peptide drug. In this work, affinity capillary electrophoresis (ACE) was developed for the identification and characterization of a chemically synthesized peptide fragment of a snake toxin called fasciculin. The affinity capillary electrophoresis technology utilized in this study employed two powerful techniques coupled on-line for the direct and rapid determination of analytes in simple and complex matrices. The first technique, aimed for the nonselective extraction and concentration of one or more analytes of interest, utilizes a solid-phase analyte concentrator device. The second technique, capillary electrophoresis, is used for the high-resolution analytical separation of the purified and concentrated target analyte(s), after elution from an analyte concentrator device. The on-line preconcentration step has proved valuable in terms of improving separation conditions as well as enhancing detection sensitivity values for the peptide fragment with a sensitivity increase ranging from 100- to 10,000-fold. Different types of analyte concentrator devices and a few binding-desorption conditions were tested. Bare and internal-wall-coated fused-silica capillaries were used. Comparative performance with HPLC in terms of selectivity and sensitivity is also discussed.

Chromatography, High Pressure Liquid↗

PubMedDate not supplied

Relationship between serum concentrations of flecainide and fluoride in humans.

The biotransformation of flecainide to serum fluoride after the oral administration of 100 mg to six healthy subjects was studied. Fluoride, flecainide acetate, calcium and alkaline phosphatase serum levels were determined at 0, 3, 4.5 and 6 hours after administration. Higher mean serum concentrations for fluoride and alkaline phosphatase (P less than 0.01, P less than 0.005) and lower mean calcium levels (P less than 0.05) were reached at 4.5 hours. The flecainide acetate serum levels ranged from 108 to 261 ng/ml. The results were analyzed for statistical significance by single factor analysis of variance with repeated measures. The Spearman rank correlation coefficient between flecainide acetate and fluoride serum increases was calculated. Our results would suggest that fluorine-containing flecainide could be biotransformed to yield some ionic fluoride which contribute to the daily fluoride intake.

Adult↗

PubMedDate not supplied

Development and validation of capillary electrophoresis methods for pharmaceutical dissolution assays.

The determination of active compounds in samples of dissolution tests of oral solid dosage forms based on the USP 23 methods was performed by capillary electrophoresis after the use of solid-phase extraction disks for the preconcentration of drugs. Enrichment factors of 20:1 allowed the determination of betamethasone and ergotamine tartrate at levels of 0.33 microgram/mL and 1.0 microgram/mL, respectively. CE analysis was performed using fused-silica capillaries (35 or 60 cm length x 75 microns i.d.) and the operating conditions consisted of 15 kV applied voltage and UV detection at 254 nm. The background electrolyte was 20-mM phosphate borate buffer, pH 9.0, containing 50 mM of sodium cholate for the separation of betamethasone and 25 mM phosphate buffer, pH 3.0, for ergotamine tartrate. Validation of the methods was also performed. Accuracy and precision of the intraday and interday assays showed comparable results with those obtained by HPLC.

Administration, Oral↗

PubMedDate not supplied

Determination of suramin by micellar electrokinetic chromatography with direct serum injection.

A simple and reproducible micellar electrokinetic chromatography (MEKC) method has been developed for the quantitation of suramin serum levels to be used for its therapeutic drug monitoring (TDM). A running buffer solution of 20 mM sodium borate, 75 mM sodium dodecyl sulfate (SDS), and 4 M urea at pH 9.2 were employed and samples were introduced directly into the capillary. The voltage applied for sample separation was 25 kV and UV detection was at 254 nm. Linearity was proved over the range 47.6 micrograms/mL-523.6 micrograms/mL of suramin (r: 0.9996). Orange G was used as internal standard and no interferences of common drugs simultaneously administered to patients were observed. Recovery values of the intraday and interday assays were between 92.5 and 97.2%.

Antineoplastic Agents↗