BackgroundA new, simple and accurate stability-indicating reverse phase high performance liquid chromatography method was developed and validated during the early stage of drug development of an oral lyophilizate dosage form of cetirizine dihydrochloride.MethodsFor RP-HPLC analysis it was used an Eclipse XDB C8 column 150 mm × 4.6 mm, 5 μm (Agilent columns, Barcelona, Spain) as the stationary phase with a mobile phase consisted of a mixture of 0.2 M K2HPO4 pH 7.00 and acetonitrile (65:35, v/v) at a flow rate of 1 mL min −1. Detection was performed at 230 nm using diode array detector. The method was validated in accordance with ICH guidelines with respect to linearity, accuracy, precision, specificity, limit of detection and quantification.ResultsThe method results in excellent separation between the drug substance and its stress-induced degradation products. The peak purity factor is >950 for the drug substance after all types of stress, which confirms the complete separation of the drug substance peak from its stress induced degradation products.Regression analysis showed r2 > 0.999 for cetirizine dihydrochloride in the concentration range of 650 μg mL −1 to 350 μg mL−1 for drug substance assay and a r2 > 0.999 in the concentration range of 0.25 μg mL−1 to 5 μg mL−1 for degradation products. The method presents a limit of detection of 0.056 μg mL −1 and a limit of quantification of 0.25 μg mL−1. The obtained results for precision and accuracy for drug substance and degradation products are within the specifications established for the validation of the method.ConclusionsThe proposed stability-indicating method developed in the early phase of drug development proved to be a simple, sensitive, accurate, precise, reproducible and therefore useful for the following stages of the cetirizine dihydrochloride oral lyophilizate dosage form development.
Introducción: El patrón de ácidos grasos (AG) de las emulsiones lipídicas (EL) utilizadas en Nutrición Parenteral (NP) condiciona diferentes respuestas fisiológicas.Objetivos: Valorar la adecuación de un protocolo clínico no restringido en la elección de EL mediante el estudio de parámetros bioquímicos y hematológicos específicos (PBHE) al inicio de la NP.Métodos: Estudio observacional retrospectivo de 4 años. Se recogieron variables demográficas, clínicas, nutricionales y analíticas al inicio de la NP. En pacientes con valores iniciales de los PBHE, se hizo un análisis univariante y multivariante para estudiar la asociación entre sus valores iniciales y el patrón lipídico utilizado.Resultados: De los 1558 pacientes, 460 pacientes (29,5%) tenían PBHE al inicio de la NP y utilizaron mayoritariamente las combinaciones soja (AS)+triglicéridos de cadena media (MCT)+oliva (AO)+pescado (AP) (37,4%) y AS+MCT+AO (35,6%). Se encontraron diferencias estadísticamente significativas en el patrón EL utilizado entre los pacientes con y sin PBHE: patrón de AG con AP 44,8% vs 39,5%, respectivamente.Las situaciones clínicas con proteína C-reactiva (PCR) elevada se asociaron con mayor uso de EL con AP: AS+AO+AP (OR:4,52 [IC 95%: 1,43-13,91] y AS+MCT+AO+AP (OR:3,34 [IC 95%: 2,10-5,33]). En situaciones clínicas complejas asociadas con paciente crítico se utilizaron EL con MCT: fracaso hepático (AS+MCT OR:2,42 [IC95%: 1,03-5,68]) y fracaso renal (AS+MCT+AP OR:3.34 [IC95%: 1,12-9.99]).Conclusiones: La inclusión protocolizada de PBHE al inicio de la NP permite complementar criterios clínicos y metabólicos en la elección de la EL.
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