The effect of lipophilicity on the hepatobiliary properties of iminodiacetic acid derivatives in the conditions of hyperbilirubinemia.

The partition coefficients (log P) of theoretically possible alkyliodinated iminodiacetic acid (IDA) derivatives and commercial IDA derivatives were calculated using two computer programs: ChemSketch Log P and ChemOffice Ultra. Newly synthesized ligands (DIETHYLIODIDA and DIISOPROPYLIODIDA) with the highest calculated log P were labeled with technetium-99m. The biodistribution and the influence of bilirubin on their biokinetics were investigated in rats and compared to corresponding results for commercial (99m)Tc-BROMIDA. Log P of (99m)Tc-complexes of synthesized ligands were determined experimentally as well as the protein binding. In comparison to (99m)Tc-BROMIDA, (99m)Tc-DIETHYLIODIDA has: (a) better biliary excretion (2.76±0.15%ID/g versus 1.83±0.10%ID/g); (b) faster hepatic clearance (2.90±0.21%ID/g versus 7.47±0.70%ID/g) and decreased biliary excretion (for 14% versus 22%) in conditions of hyperbilirubinemia after 15min. It is proved that (99m)Tc-DIISOPROPYLIODIDA has a prolonged hepatic transit time and decreased biliary excretion.

Study of valsartan interaction with micelles as a model system for biomembranes.

In this study, the interaction of valsartan (VAL), an angiotensin II receptor antagonist, with cationic surfactant cetyltrimethylammonium bromide (CTAB) was investigated. The effect of cationic micelles on spectroscopic and acid-base properties of VAL was carried out using UV spectrophotometry at physiological conditions (pH 7.4). The binding of VAL to CTAB micelles implied a shift in drug acidity constant (pK(a)(water)-pK(a)(micelle)=1.69) proving the great affinity of VAL dianion for the positively charged CTAB micelle surface. To quantify the degree of VAL/CTAB interaction, two constants were calculated by using mathematical models: micelle/water partition coefficient (K(x)) and drug/micelle binding constant (K(b)). The decrease of K(x) with VAL concentration, obtained by using pseudo-phase model, is consistent with an adsorption-like phenomenon. From the dependence of differential absorbance at lambda=295 nm on CTAB concentration, by using mathematical model that treats the solubilization of VAL dianion as its binding to specific sites in the micelles (Langmuir adsorption isotherm), the binding constant (K(b)=(2.50+/-0.49)x10(4)M(-1)) was obtained. Binding constant VAL/CTAB was also calculated using micellar liquid chromatography (MLC).

Determination of fluocortolone pivalate and fluocortolone hexanoate in suppositories using reverse-phase HPLC.

Fluocortolone and its esters are synthetic corticosteroids used topically in the treatment of various skin disorders. A method that can be successfully used for the separation and determination of fluocortolone pivalate and fluocortolone hexanoate in suppositories was developed. This method is based on reverse-phase HPLC on Supelcosil LC-18 (25 cm x 4.6 mm, 5 microns), using methanol-acetonitrile-water-glacial acetic acid (17:46:37:0.4 v/v/v/v) as mobile phase at a flow rate of 3.0 ml/min. Detection was carried out using a UV detector at 238 nm. The method developed was validated, and calibration curves were established dependent on peak area. The validated ranges for fluocortolone pivalate and fluocortolone hexanoate are 15-305 micrograms/ml (r = 0.9995) and 15-315 micrograms/ml (r = 0.9996), respectively. The limits of detection and the limits of quantification for both esters were also determined.

Spectrophotometric determination of desoximetasone in ointment using 1,4-dihydrazinophthalazine.

The proposed method is based on coloured hydrazone formation with 1,4-dihydrazinophthalazine as a reagent. Heating at 85 degrees C for 2 h was found necessary to ensure optimal hydrazone formation in the presence of hydrochloric acid. The yellow hydrazone product has an absorption maximum at 380 nm. A linear relationship between absorbance and concentration was established in the concentration range 3.19 x 10(-6) -3.19 x 10(-5) mol l-1 (the regression equation was y = 0.013 167 3 + 0.019 025 9x; correlation coefficient r = 0.9991; n = 6). The detection limit was 1.2 micrograms ml-1 (molar absorptivity found was 1.97 x 10(4) l mol-1 cm-1). The reliability of the proposed method was checked at three different concentrations; the relative standard deviation (RSD) varied from 1.03 to 2.01%. The described method applied to the determination of desoximetasone in ointment gave precise and reproducible results; the recovery was 98.55% with RSD = 2.40% (n = 10).