Hana Tománková

Study of the time dependence of the stability of 5-aza-2′-deoxycytidine in acid medium

Abstract The stability of a solution of AzDC in acid medium (0.1 N HCl) was studied using thinlayer chromatography on cellulose. The Rf values of AzDC and its decomposition products are given in Table 1. The time course of the hydrolytic decomposition of AzDC in acid medium was studied on the basis of the decrease in the amount of AzDC. The amount of AzDC was quantitatively evaluated densitometrically at certain time intervals after chromatographic separation (Figs. 1, 2). After 10 hr the content of AzDC decreased from 100% at the beginning of the experiment to 23%; t 2 (decomposition half-time) was found to be between 3.5 and 3.7 hr (Table 2, Fig. 3).

Determination of parabens and their degradation product p-hydroxy-benzoic acid in pharmaceutical dosage forms by HPTLC densitometry

Abstract HPTLC densitometry has been developed for the determination of parabens and their degradation product p-hydroxybenzoic acid in pharmaceutical preparations. The method was used for simultaneous determination of parabens in combination:methylparaben - propylparaben, propylparaben - butylparaben and for the determination their stability in dosage forms (suspensions, ointment). The substances were separated on silica gel with fluorescence indicator in system n-pentane - glacial acetic acid (88:12, v/v). Absorbance measurements(detection of reflectance) of separated parabens was carried out “in situ” at 256 nm using single-level calibration (external standard). For the determination of p-hydroxybenzoic acid, a five-level calibration curve (external standard) was used in the concentration range of 20–100 ng/band. The results were evaluated by linear regression analysis. The relative standard deviation values (R.S.D.%) were in range 1.24–1.89 %.

Study of the stability of pyrimidine series cytostatics, ftorafur and fluorouracil injections

Abstract The stability of the cytostatics, ftorafur and fluorouracil injections, was studied in dependence on irradiation with UV light and on the medium temperature and pH. In the first stage of the thermal and photochemical decomposition of ftorafur, tetrahydrofuran dissociated from position N1 in the pyrimidine ring and 5-fluorouracil was formed. In the second stage of the thermal and photochemical decomposition of ftorafur, the pyrimidine ring opened between N3 and C4 and between C6 and N1, with formation of urea. Ftorafur, fluorouracil, and urea were determined using thin-layer chromatography and spectrophotometry in the UV and visible region.

The oxidation of aminophenazone by hydrogen peroxide

Abstract Aqueous solutions of aminophenazone were oxidized by excess hydrogen peroxide in acidic, neutral and alkaline media and the reaction was followed using thin-layer chromatography and spectrophotometry in the visible and uv regions. The oxidation course is explained on the basis of detection of the products formed (4-methylaminoantipyrine, 4-aminoantipyrine, 1-phenyl-3-methyl-4-(phenylazo)-5-pyrazolone, 1-acetyl-1-methyl-2-di-methyl-oxanil-2-phenylhydrazine, oxalic acid, dimethylamine).

The M2 muscarinic receptors are essential for signaling in the heart left ventricle during restraint stress in mice

Abstract We hypothesized that muscarinic receptors (MRs) in the heart have a role in stress responses and thus investigated changes in MR signaling (gene expression, number of receptors, adenylyl cyclase (AC), phospholipase C (PLC), protein kinase A and C (PKA and PKC) and nitric oxide synthase [NOS]) in the left ventricle, together with telemetric measurement of heart rate (HR) in mice (wild type [WT] and M2 knockout [KO]) during and after one (1R) or seven sessions (7R) of restraint stress (seven mice per group). Stress decreased M2 MR mRNA and cell surface MR in the left ventricle in WT mice. In KO mice, 1R, but not 7R, decreased surface MR. Similarly, AC activity was decreased in WT mice after 1R and 7R, whereas in KO mice, there was no change. PLC activity was also decreased after 1R in WT and KO mice. This is in accord with the concept that cAMP is a key player in HR regulation. No change was found with stress in NOS activity. Amount of AC and PKA protein was not changed, but was altered for PKC isoenzymes (PKCα, β, γ, η and ε (increased) in KO mice, and PKCι (increased) in WT mice). KO mice were more susceptible to stress as shown by inability to compensate HR during 120 min following repeated stress. The results imply that not only M2 but also M3 are involved in stress signaling and in allostasis. We conclude that for a normal stress response, the expression of M2 MR to mediate vagal responses is essential.

A TLC-densitometric determination of sulphonamide chemotherapeuticals

Abstract A selective, sensitive, rapid and well reproducible TLC-densitometric method has been developed for simultaneous determination of sulphonamides (sulfamethoxazol, sulfadoxin, sulfamerazin, sulfametrol, sulfadiazin) in combination with trimethoprim in various dosage forms. The R. S. D. (%) is 1.09 to 1.82 for the sulphonamides and 1.1 for trimethoprim. The method is suitable not only for quantitative evaluation of sulphonamides and trimethoprim in all commercial drug forms (tablets, injections, suspensions, syrups, pulvis), but also for checking the identity of the active substances.

A study of the stability of pyrimidine series cytostatics, Ftorafur and 5-fluorouracil: The effect of oxidation on the stability of Ftorafur and 5-fluorouracil

Abstract The stability of 1% solutions of cytostatics Ftorafur and 5-fluorouracil was studied during oxidation with hydrogen peroxide in alkaline (0.1 N NaOH), acidic (0.1 N H2SO4), and weakly acidic (pH 5) solutions by thin-layer chromatography. The decrease in the cytostatic content was monitored spectrophotometrically in the uv region. The greatest decrease in the cytostatic content occurred in alkaline solutions, where the pyrimidine ring opened between N3 and C4 and between C6 and N1, with formation of urea.

An analytical study of Benfluron hydrochloride

Abstract The physical and chemical properties of the cytostatically active substance, Benfluron · HCl (5-(2-dimethylaminoethoxy)-7-oxo-7H-benzo[c]fluorene hydrochloride), were studied. The results (IR and UV spectrophotometry, acidimetry in nonaqueous protogenic medium, thin-layer chromatography) were used to characterize the pharmaceutical, to determine it, and to monitor its purity and stability.

A study of the stability of 5-aza-2′-deoxycytidine in alkaline media in dependence on time

Abstract It has been determined that the first stage of the hydrolytic degradation of the cytostatically active substance, 5-aza-2′-deoxycytidine (AzDC), in alkaline solution yields N -amidinium- N′ -(2-deoxy-β- d -erythropentofuranosyl) urea formate (AUF) due to the opening of the triazine ring between C6 and N1. In the second stage of the hydrolytic degradation, the -NHCO- bond in AUF is opened at an elevated temperature with formation of guanidine. The reaction mechanisms are given. The degradation was monitored using thin-layer chromatography and the standard substances of AUF and guanidine. HCl were prepared synthetically.

An analytical study of 5-Aza-2′-deoxycytidine

Abstract The chemical and physical properties of the cytostatically active substance, 5-aza-2′-deoxycytidine, were studied. The results obtained (uv and ir spectrometry, [α] D 22 , TLC with densitometirc evaluation, determination of N) can be used for characterization of the substance, for its determination, and for the monitoring of the substance purity and stability.