Citalopram Hydrobromide: degradation product characterization and a validated stability-indicating LC-UV method

Abstract

Cinco produtos de degradação (I-V) do hidrobromidrato de citalopram (CTL) foram formados sob condições diferentes de degradação forçada. Os produtos I e II foram formados sob condições hidrolíticas, enquanto que os produtos III-V sob condições fotolíticas. Os produtos II e IV foram encontrados como impurezas conhecidas, citalopram carboxamida e citolopram-N-óxido, respectivamente. O produto I foi encontrado como sendo uma nova impureza, que foi caracterizada como 3-hidroxicitalopram N-óxido. A droga e todos os cinco produtos de degradação foram resolvidos de uma maneira otimizada em uma coluna C 8 com fase móvel composta de acetonitrila e tampão acetato de amônia (pH* 4,5) na vazão de 0,50 mL min -1 . O método foi linear, preciso com RSD < 3 (desvio padrão relativo) e exato com recuperação de 88-97% no intervalo de concentração 5-500 mg mL -1 de citalopram. Os limites de determinação (LOD) e de quantificação (LOQ) foram 1 mg mL -1 e 5 mg mL -1 , respectivamente. A análise por arranjo de fotodiodo de uma solução da droga degradada contendo a droga e todos os cinco produtos de degradação revelou picos isolados, puros. Sendo assim, o método pode ser sugerido como estável.Five degradation products (I-V) of citalopram hydrobromide (CTL) were formed under different forced degradation conditions. Products I and II were formed under hydrolytic conditions while product III-V were formed under photolytic conditions. Products II and IV were found known impurities as citalopram carboxamide and citalopram N-oxide, respectively. Product I was found to be a new impurity which was characterized as 3-hydroxycitalopram N-oxide. The drug and all five degradation products were optimally resolved on a C 8 column with mobile phase composed of acetonitrile and ammonium acetate buffer (pH* 4.5) flowing at a rate of 0.50 mL min -1 . The method was linear, precise RSD < 3 (relative standard deviation) and accurate (recovery being 88-97%) in the concentration range of 5-500 mg mL -1 of citalopram. The limits of detection (LOD) and of quantitation (LOQ) were 1 mg mL -1 and 5 mg mL -1 , respectively. The photodiode array (PDA) analysis of the degraded CTL solution containing the CTL and all five degradation products revealed each peak to be pure. Hence, the method was suggested to be stability-indicating.

Utility of eosin Y as a complexing reagent for the determination of citalopram hydrobromide in commercial dosage forms by fluorescence spectrophotometry

“…The performance of the proposed method has been compared with other existing methods with regard to linear range, LOD and LOQ values (Table ). LC‐UV and capillary zone electrophoresis methods are expensive and their LOD values are 1 and 0.8 μg/mL, respectively. Moreover, RP‐HPLC has a wider linear range, but the lower limit starts at 25 μg/mL, which is not acceptable.…”

LC-MS characterization of valsartan degradation products and comparison with LC-PDA

“…HPLC-PDA and HPLC-UV are the primary stability-indicating methods used to monitor impurities/DP during stress testing and storage (Alsante et al, 2003). Although these techniques seem efficient for a variety of degradation studies (Thomas et al, 2012;Sharma et al, 2011;Bansal et al, 2008), they may fail to detect products lacking a chromophore group (Bansal et al, 2008) or with co-eluting sets of degradation products which may even co-elute with the parent drug and lead to false stability results.…”

CHARACTERIZATION OF AN UNKNOWN IMPURITY IN CITALOPRAM HYDROBROMIDE ACTIVE PHARMACEUTICAL INGREDIENT BY SEMI-PREPARATIVE ISOLATION AND LC-ESI/MSnAND NMR

“…Citalopram was found to degrade in all the ICH prescribed conditions in a solution state. [26] There are many reports on detection, isolation and characterization of trace level process-related impurities in citalopram bulk drug. [25][26][27][28][29][30] In this study, an unknown impurity in the range of 0.25% was observed in a laboratory sample by USP method-I and method-II.…”

“…LC-MS n study confirmed that this impurity was different from previously reported impurities. [25][26][27][28][29][30] Structure of unknown impurity was proposed based on MS n data. Impurity was isolated using semi-preparative HPLC followed by characterization using IR, NMR and EA analysis.…”