Cefazolin concentration in the mediastinal adipose tissue of patients undergoing cardiac surgery

Abstract Objective: To measure the concentration of cefazolin in the anterior mediastinal adipose tissue of patients undergoing cardiac surgery, determining the variation of cefazolin concentration. Methods: Two samples of approximately 1g of subcutaneous tissue were collected from 19 patients who underwent surgery in December 2015: the first sample was collected right after sternotomy and the second one, before sternal synthesis with steel wires. Antibiotic dosage was administered through high performance liquid chromatography. Results: We observed a positive and statistically significant correlation between time 1 and cefazolin concentration (r=0.489 and P=0.039). For time 2 and cefazolin concentration, there was a negative and statistically significant correlation between both variables (r=-0.793 and P<0.001). A negative correlation was also observed between body mass index and cefazolin concentration at time 2 (r=-0.510 and P=0.031). The regression model showed that every 1-minute increase in time 1 corresponded to an increase of 0.240 µg/dL in cefazolin concentration, whereas every 1-minute increase in time 2 corresponded to a reduction of 0.046 µg/dL in cefazolin concentration. As for body mass index, every 1 kg/m2 increase corresponded to a reduction of about 0.510 µg/dL in cefazolin concentration. Conclusion: There was a positive and significant correlation between the initial time of surgery and cefazolin level in the first dosage. The evaluation of the second dosage showed a negative and significant correlation between cefazolin level and the second time of dosage. The concentration of cefazolin is under the influence of body mass index.

Validation of analytical methodology for quantification of cefazolin sodium pharmaceutical dosage form by high performance liquid chromatography to be applied for quality control in pharmaceutical industry

A reversed-phase high performance liquid chromatography method was validated for the determination of cefazolin sodium in lyophilized powder for solution for injection to be applied for quality control in pharmaceutical industry. The liquid chromatography method was conducted on a Zorbax Eclipse Plus C18 column (250 x 4.6 mm, 5 μm), maintained at room temperature. The mobile phase consisted of purified water: acetonitrile (60: 40 v/v), adjusted to pH 8 with triethylamine. The flow rate was of 0.5 mL min-1 and effluents were monitored at 270 nm. The retention time for cefazolin sodium was 3.6 min. The method proved to be linear (r2=0.9999) over the concentration range of 30-80 µg mL-1. The selectivity of the method was proven through degradation studies. The method demonstrated satisfactory results for precision, accuracy, limits of detection and quantitation. The robustness of this method was evaluated using the Plackett–Burman fractional factorial experimental design with a matrix of 15 experiments and the statistical treatment proposed by Youden and Steiner. Finally, the proposed method could be also an advantageous option for the analysis of cefazolin sodium, contributing to improve the quality control and to assure the therapeutic efficacy.

Um método cromatográfico em fase reversa foi validado para a determinação de cefazolina sódica em pó liofilizado, a ser aplicado no controle de qualidade em indústrias farmacêuticas. O método por cromatografia líquida foi conduzido em coluna Zorbax Eclipse Plus C18 (250 × 4,6 mm, 5 µm) mantida à temperatura ambiente. A fase móvel consistiu de água purificada: acetonitrila (60 : 40 v/v), com o pH ajustado para 8 com trietilamina. A vazão usada foi de 0,5 mL min-1 e os analitos de interesse foram monitorizados a 270 nm. O tempo de retenção da cefazolina sódica foi de 3,6 min. As áreas dos picos de cefazolina sódica foram lineares na faixa de concentração de 30-80 µg mL-1 (r2 = 0,9999). A seletividade do método foi demonstrada através de estudos de degradação. O método demonstrou resultados satisfatórios para precisão, exatidão, limites de detecção e de quantificação. A robustez do método foi avaliada utilizando o esquema fatorial de Plackett-Burman com uma matriz de 15 experimentos simultâneos, e analisados por tratamento estatístico proposto por Youden e Steiner. Finalmente, o método proposto pode ser também uma opção de êxito para a análise de cefazolina sódica, contribuindo para o controle de qualidade e para garantir a eficácia terapêutica.