ABSTRACT
A stability-indicating high-performance liquid chromatography procedure has been developed for the determination of alizapride (AL) and its main degradation products alizapride carboxylic acid (AL-CA) and alizapride N-oxide (AL-NO2) in drug substance and product. The method was developed based on forced degradation data obtained by HPLC-MS analysis. Indeed AL underwent chemical degradation by acid/base catalyzed hydrolysis and oxidation the main degradation products being AL-CA and AL-NO2 respectively. The separation and quantisation were achieved on a 150-mm reverse phase column with a hydrophilic linkage between silica particles and hydrophobic alkyl chains. The mobile phase was constituted (flow rate 1.5mLmin(-1)) of eluant A: aqueous acetate buffer (pH 4.0; 20mM) and eluant B: CH(3)OH using a gradient elution and detection of analytes at 225nm. The method showed good linearity for the AL, AL-CA, AL-NO2 mixture in the 25-75, 1-15 and 1-15microgmL(-1) ranges respectively, being all the square of the correlation coefficients greater than 0.999. The precision, determined in terms of intra-day and inter-day precisions and expressed as RSDs were 0.8, 1.3 and 2.1% and 1.0, 1.7, 4.8% for AL, AL-CA and AL-NO2 respectively. The method demonstrated also to be accurate; indeed the average recoveries, at 100% and 0.2% of the target assay concentration, were 100.5, 98.6, and 96.8% for AL, AL-CA and AL-NO2 respectively. The robustness was also evaluated by variations of mobile phase composition and pH. Finally, the applicability of the method was evaluated in commercial dosage form analysis as well as in stability studies.
Subject(s)
Antiemetics/chemistry , Chromatography, High Pressure Liquid , Pyrrolidines/chemistry , Spectrophotometry, Ultraviolet , Technology, Pharmaceutical/methods , Carboxylic Acids/chemistry , Catalysis , Chemistry, Pharmaceutical , Chromatography, High Pressure Liquid/standards , Dosage Forms , Drug Stability , Hydrogen-Ion Concentration , Hydrolysis , Oxidation-Reduction , Oxides/chemistry , Reproducibility of Results , Spectrophotometry, Ultraviolet/standards , Technology, Pharmaceutical/standardsABSTRACT
The potential interactions between rabeprazole, a widely used proton pump inhibitor, and anticancer drugs (5-fluorouracil, docetaxel, cyclophosphamide, gemcitabine, methotrexate, doxorubicin, etoposide) or drugs commonly present in the therapy of oncological patients (fluoxetine and ondansetron), were studied using in vitro human liver microsomes. The interactions between rabeprazole and the anticancer drugs were evaluated by measuring their concentrations in test and control incubations with HPLC-DAD-UV methods. To achieve this aim, nine HPLC-DAD-UV methods were developed using different stationary and mobile phases. The methods were then validated for the following parameters: selectivity, linearity, precision, and accuracy. As expected rabeprazole did not significantly inhibit the metabolism of the evaluated drugs in human liver microsomal preparations at the selected concentrations. These results shows that rabeprazole probably could be devoid of pharmacokinetic interactions with common drugs used during chemotherapy.
Subject(s)
2-Pyridinylmethylsulfinylbenzimidazoles/pharmacology , Antineoplastic Agents/pharmacology , Enzyme Inhibitors/pharmacology , Microsomes, Liver/drug effects , Antibiotics, Antineoplastic/pharmacology , Antidepressive Agents, Second-Generation/pharmacology , Antiemetics/pharmacology , Antimetabolites, Antineoplastic/pharmacology , Antineoplastic Agents, Alkylating/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Chromatography, High Pressure Liquid , Cyclophosphamide/pharmacology , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Docetaxel , Doxorubicin/pharmacology , Etoposide/pharmacology , Female , Fluorouracil/pharmacology , Fluoxetine/pharmacology , Humans , In Vitro Techniques , Indicators and Reagents , Male , Methotrexate/pharmacology , Ondansetron/pharmacology , Rabeprazole , Reference Standards , Taxoids/pharmacology , GemcitabineABSTRACT
A simple and efficient method for the determination of isopropyl-9H-thioxanten-9-one (ITX) in different fat content milk samples and baby milk samples stored in packaged cartons was developed and validated. Samples were extracted using solid-phase extraction (SPE) and analysed by gas chromatography-tandem mass spectrometry operated in selected reaction monitoring mode (SRM). Validation was carried out in terms of limit of detection (LOD), limit of quantitation (LOQ), linearity, precision and trueness. LOD and LOQ values in the low microg/L were achieved, whereas linearity was established within 0.5-500 microg/L range. Good precision was obtained both in terms of intra-day repeatability and inter-day precision on two concentration levels (RSD% lower than 2%). Good percentage recoveries were obtained (92.0-102.0%) even in the presence of high amount of fat. Finally, the developed method was successfully applied to analyse a number of commercial milk samples with different fat content and baby milk samples.
