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EN
An enantioselective HPLC method was developed and validated for the separation and the estimation of citalopram (CIT) enantiomers in bulk drug and pharmaceutical preparations. The method was validated for its linearity (correlation coefficient = 0.9994 and 0.996 for S-(+)-enantiomer and R-(−)-enantiomer, respectively), accuracy, robustness, and intermediate precision. Experimental design was applied during intermediate precision (full factorial 2 3 design) and robustness testing (Box Benken as a factorial design), for robustness test three factors were considered: percentage of organic modifier, flow rate, and temperature. The separation was achieved on cellulose tris(phenylcarbamate) known as Chiralcel® OC (25 cm, 4.6 mm i.d.) derivatized cellulose (phenyl carbamate), with UV detection at 245 nm using n-hexane-isopropanoldiethylamine (85:15:0.2, υ/υ/υ) as mobile phase at flow rate 0.7 mL min−1. A decrease in the flow rate results in decreasing the selectivity factor (α), while varying the percentage of n-hexane and the temperature have no effect on selectivity factor (α). For intermediate precision, the variables considered were analyst, equipment, and day. The RSD% value (0.73%, n = 24) indicates a good precision for the analytical procedure. The method was found to be suitable for determination of enantiomeric purity of CIT in bulk drugs and pharmaceutical formulations.
EN
Using extracellular recording we studied changes in the reactivity of rat frontal cortical slices to the 5-HT1A, 5-HT2 and 5-HT4 receptor agonists, (±)-2-dipropyloamino-8-hydroxy-1,2,3,4-tetrahydronaphtalene hydrobromide (8-OH-DPAT), (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) and zacopride, respectively, induced by an earlier treatment of animals with corticosterone lasting 1 or 3 weeks. Spontaneous bursting activity was recorded in ex vivo slices incubated in a medium devoid of Mg2+ ions and containing picrotoxin (30 µM). Repetitive, but not single, corticosterone administration resulted in an attenuation of the effect of the activation of 5-HT1A receptors and in an enhancement of the effect related to 5-HT2 receptors. The effect of 5-HT4 receptor activation remained unchanged. In separate two sets of experiments rats were treated with corticosterone for 3 weeks and additionally with imipramine or citalopram, beginning on the eighth day of corticosterone administration. In the corticosterone plus imipramine as well as corticosterone plus citalopram groups the effects of 8-OH-DPAT and DOI were not different from control indicating that corticosterone-induced functional modifications in the reactivity of 5-HT1A and 5-HT2 receptors were reversed by antidepressant treatments.
EN
Simple and robust HPLC methods for direct separation of enantiomers of popular antide-pressive drugs: fluoxetine and citalopram have been developed. Enantioseparation has been performed on several commercial chiral HPLC columns. Composition of the mobile phase has been optimised. For the separation of fiuoxetine and citalopram enantiomers amylose Chiralpak AD column and cellulose Chiralcel OD-H column were the most convenient, respectively. The limits of quantitation for fluoxetine and citalopram were found to be 0.02 mg mL-1 and 0.003 mg mL-1, respectively. The proposed methods have been validated under the applied conditions. They have been found to be selective and precise with linear response of detector for both pairs of enantiomers.
PL
Opracowano prostą i odporną na zakłócenia metodę bezpośredniego oznaczania enancjomerów popularnych leków przeciwdepresyjnych fluoksetyny I cytalopramu. Enancjoseparacje przeprowadzono za pomocą szeregu handlowo dostępnych kolumn Chiralpak AD i Chiralcel OD-H. Do rozdzielania fluoksetyny najbardziej odpowiednia okazała się kolumna amylozowa Chiralpak AD. a do cytalopramu kolumna celulozowa Chiralcel OD-H. Granica oznaczalności d!a fluoksetyny i cytalopramu wynosi odpowiednio 0.02 mg mL-1 i 0.003 mg ml-1. Proponowane metody zostały zwalidowane dla wybranych parametrów rozdzielania. Okazały się one selektywne i precyzyjne z liniową odpowiedzią detektora dla obu par enancjomerów.
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