Quantification and stress degradation studies of cefepime/tazobactam in dry injection form by an RP-HPLC method

Abstract

A simple, specific, precise, accurate, linear, rapid, economic and validated stability indicating an RP-HPLC method for the simultaneous quantification of cefepime and tazobactam in a dry injection dosage form has been developed. Separation was performed on a 5 µm ACE C 18 column with phosphate buffer, pH adjusted to 4.5 with phosphoric acid: methanol (70:30) at a flow rate of 1 mL/min and at a temperature of 25 °C. Regression analysis showed linearity at a detector wavelength of 290 nm in the range of 200-600 μg/mL for cefepime and 25-75 μg/mL for tazobactam. All of the analytes were adequately resolved with acceptable tailing. The percentage content found for cefepime was 99.98% and of tazobactam was 99.49% in the parenteral formulation. The method was validated in terms of linearity, precision, accuracy, specificity, robustness and system suitability according to ICH guidelines. Stress degradation studies were performed on the placebo and drug products, drugs of interest were well resolved from the degradation products. The developed method was effectively applied for the simultaneous quantification of cefepime and tazobactam in a dry injection formulation. Desenvolveu-se método específico, preciso, exato, linear, rápido e econômico, de validação de estabilidade, indicando o método de CLAE-FR para a quantificação simultânea de cefepima e tazobactam na forma de dosagem injetável seca. A separação foi realizada em coluna C18 de ACE 5 mM com tampão fosfato, pH ajustado para 4,5 com ácido fosfórico:metanol (70:30), em fluxo de 1 mL/min e temperatura de 25 °C. A análise de regressão mostrou linearidade no detector de comprimento de onda de 290 nm, na faixa de 200-600 μg/mL, para cefepima, e 25-75 μg/mL, para tazobactam. Todos os analitos foram, adequadamente, resolvidos com cauda aceitável. O teor percentual encontrado na formulação parenteral foi de 99,98%, para cefepima, e de 99,49%, para o tazobactam. O método foi validado em termos de linearidade, precisão, exatidão, especificidade, robustez e adequação do sistema de acordo com as diretrizes ICH. Estudos de degradação por estresse foram realizados no grupo placebo e nos medicamentos e os fármacos de interesse foram bem resolvidos a partir dos produtos de degradação. O método desenvolvido foi efetivamente aplicado para quantificação simultânea de cefepima e tazobactam na formulação injetável seca.Uniterms: CLAE-FR. Cromatografia líquida de alta eficiência/fase reversa/análise quantitativa. Cefepima/ quantificação. Tazobactam/quantificação. Formulação injetável seca/análise quantitativa. Formulações farmacêuticas/estudo de degradação.

Reversed‐phase high‐performance liquid chromatography analytical method development and validation for cefepime and sulbactam injection formulation assay: A quality by design approach

“…Finding the most important factors that influenced the features of the liquid-liquid chromatographic separation, such as retention time, relative retention time, peak form and symmetry, tailing factor, and the number of theoretical plates, was one of the goals of this study [13][14][15]. A literature survey revealed that several methods are available for the determination of cefepime in different matrixes individually or in combination with other drugs like second-derivative spectroscopy [16], HPLC [17][18][19], and UPLC [20]. Sulbactam was successfully determined by CITP [21], UV-spectrophotometric [22], and HPLC [23][24][25][26].…”

Stability indicating UPLC-MS/MS method for quantification and identification of cefepime and its degradants in API

“…It is used to treat urinary tract infections, septicemia, staphylococcal infections, bronchitis, intra-abdominal infections, skin and its structures infections, pneumonia infections, and in febrile neutropenic patients (Glish and Burinsky, 2008;Lemke et al, 2002). CFP stability was estimated using several methods using chromatography (Abd El Aziz Shama et al, 2021;Al Kamaly, 2022;Bjergum et al, 2021;De Borba et al, 2008;Dos Anjos et al, 2022;El-Beltagy et al, 2019;El-Dars et al, 2019;Fage et al, 2021;Isla et al, 2005;Jagadeesh Kumar et al, 2010;Jiang et al, 2010;Jiménez Palacios et al, 2005;Kalyani et al, 2018;Kommana et al, 2014;Liu et al, 2018;Mameli et al, 2019;Moorthy et al, 2020;Nemutlu et al, 2009, Ocaña González et al, 2004Ohmori et al, 2011;Patil et al, 2018;Rehm and Rentsch, 2020;Rodrigues et al, 2016;Seraisso et al, 2022;Shrestha et al, 2014;Siddiqui et al, 2010;Sun et al, 2022;Sundara Raj et al, 2013;Sunitha et al, 2013;Van Vooren and Verstraete, 2021;Zander et al, 2015) but these methods had some disadvantages as complex mobile phase composition, increased matrix effect, decreased sensitivity, and inability to identify degradants using trace analysis in addition to fragmentation (Niessen, 2010;Niessen and Ricardo, 2017), less environmentally friendly, and time-consuming. However, there have been no previous analytical procedures of trace analysis reported on CFP stability studi...…”