Stability of ceftolozane in human plasma and dried blood spots: Implications for transport and storage

Ceftolozane is a newer β-lactam antibiotic drug effective against gram-negative pathogens. Its pharmacokinetic parameters are dominated by the patients' kidney function. Consequently, in patients with impaired kidney function or those who are treated with different forms of renal replacement therapy, therapeutic drug monitoring (TDM) of ceftolozane is strongly recommended to enhance safety and efficiency of the antibiotic treatment. Various methods for the quantification of ceftolozane in plasma samples have been described utilizing HPLC-UV or LC-MS/MS. However, all these methods are impaired by the instability of ceftolozane in plasma samples. In this work, we have determined the stability of ceftolozane in human plasma at temperatures of 40 °C, 23 °C, 6 °C and - 20 °C. At 6 °C and - 20 °C, ceftolozane was stable in human plasma over the observed time range of 7 days. At 23 °C and 40 °C, plasma samples were of acceptable (i.e. less than 15% decay) stability over time ranges of 71.2 h and 5.6 h, requiring expedited sample transport to the laboratory. Dried blood spots (DBS) were reported in the literature as matrix with beneficial properties regarding stabilities of β-lactam antibiotics. However, in this study we found that ceftolozane was of inferior stability in this matrix in comparison to plasma. Thus, DBS cannot be recommended as matrix for ceftolozane in TDM.