Development and validation of a stability-indicating HPLC-UV method for the determination of alizapride and its degradation products

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.

In vitro metabolic fate of alizapride: evidence for the formation of reactive metabolites based on liquid chromatography‐tandem mass spectrometry

“…Alizapride hydrochloride ( AL ) was obtained as gift sample from Pharmafar S.r.l. (Torino, Italy); 6‐methoxy‐1 H ‐benzotriazole‐5‐carboxylic acid 1 and 6‐methoxy‐ N ‐{[1‐oxy‐1‐(prop‐2‐en‐1‐yl)pyrrolidin‐2‐yl]methyl}‐1 H ‐benzotriazole‐5‐carboxamide (diastereomers A 4 and B 5) were synthesized according to the procedure cited in the literature . 6‐Hydroxy‐ N ‐{[1‐(prop‐2‐en‐1‐yl)pyrrolidin‐2‐yl]methyl}‐1 H ‐benzotriazole‐5‐carboxamide 6 was synthesized as previously reported …”

“…(Torino, Italy); 6-methoxy-1H-benzotriazole-5-carboxylic acid 1 and 6-methoxy-N-{[1-oxy-1-(prop-2-en-1-yl)pyrrolidin-2-yl]methyl}-1Hbenzotriazole-5-carboxamide (diastereomers A 4 and B 5) were synthesized according to the procedure cited in the literature. [14] 6-Hydroxy-N-{[1-(prop-2-en-1-yl)pyrrolidin-2-yl]methyl}-1H-benzotriazole-5-carboxamide 6 was synthesized as previously reported. [15]…”

Long term stability of an admixture of alizapride and ondansetron in 0.9% sodium chloride solution polyolefin bags stored at 5±3°C

“…The stability of alizapride has already been tested alone or in association with different drugs. [3][4][5][6] As well, the stability of ondansetron alone has been challenged in different containers, 7 at different temperature 8 and in association with various drugs. [9][10][11] Thoses studies showed a stability up to 3 months for ondansetron and up to 32 days for alizapride in several conditions.…”

Development and validation of an ultra-performance liquid chromatography method coupled with tandem mass spectrometry for determination of alizapride in human plasma

“…Most of the reported methods for determination of ALZ use liquid-liquid extraction [2][3][4]6,7 or lack IS. 6,7 Tamaro et al 8 reported an HPLC method with UV detection for the determination of ALZ in drug powder and drug product. Sample preparation method is a key step in bioanalytical method development that leads to improved selectivity and sensitivity.…”