Laboratori Clínic Department, IDIBELL, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
Infectious Diseases Department, IDIBELL, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
Clin Chim Acta. 2019 Jan;488:50-60. doi: 10.1016/j.cca.2018.10.034. Epub 2018 Oct 30.
Ceftolozane, in combination with the β-lactamase inhibitor tazobactam, is a new option in the pipeline against multidrug-resistant Gram-negative bacilli. As for other β-lactam antibiotics, optimizing the use of ceftolozane-tazobactam is advisable, especially in difficult-to-treat infections. In this regard, therapeutic drug monitoring would be required to guide the treatment of ceftolozane-tazobactam. Thus, we aimed to develop and validate procedures based on UHPLC-MS/MS for measurement of ceftolozane and tazobactam plasma concentrations in clinical practice.
Analyses were conducted using an Acquity® UPLC® integrated system coupled to an Acquity® TQD® tandem-quadrupole mass spectrometer. Ceftolozane, tazobactam and their internal standards (ceftazidime-D and sulbactam) were detected by electrospray ionization mass spectrometry in positive and negative ion multiple reaction monitoring modes, using transitions of 667.2 → 199.3/139.0 and 551.9 → 467.9 for ceftolozane and ceftazidime-D, and 299.0 → 138/254.9 and 232.0 → 140.0 for tazobactam and sulbactam. Measurement procedures developed were used for guiding the treatment and adjusting daily dose of ceftolozane-tazobactam in patients with osteoarticular infections.
Coefficients of variation and absolute relative biases were <7.9% and 6.5% in all cases. The lower limit of quantification, linearity, normalized-recoveries, normalized-matrix effects and measurement uncertainties for ceftolozane were: 0.97 mg/L, (0.97-125) mg/L, ≤113.6%, ≤108.7%, and ≤ 18.7%, respectively; and for tazobactam: 1.04 mg/L, (1.04-125) mg/L, ≤103.6%, ≤101.9%, and ≤ 20.0%. No interferences and carry-over were observed. Patients plasma concentrations were higher than the recommended 3-4 times the minimal inhibitory concentrations.
Our measurement procedures are suitable for therapeutic drug monitoring of ceftolozane-tazobactam in patients with osteoarticular infections.
头孢洛扎他唑巴坦是一种新的多药耐药革兰氏阴性杆菌治疗选择，与β-内酰胺酶抑制剂他唑巴坦联合使用。与其他β-内酰胺类抗生素一样，优化头孢洛扎他唑巴坦的使用是明智的，尤其是在治疗困难的感染时。在这方面，需要治疗药物监测来指导头孢洛扎他唑巴坦的治疗。因此，我们旨在开发和验证基于 UHPLC-MS/MS 的程序，以在临床实践中测量头孢洛扎他唑巴坦和他唑巴坦的血浆浓度。
使用 Acquity® UPLC® 集成系统与 Acquity® TQD® 串联四极杆质谱仪进行分析。头孢洛扎他唑巴坦、他唑巴坦和内标物（头孢他啶-D 和舒巴坦）通过电喷雾电离质谱在正、负离子多反应监测模式下检测，头孢洛扎他唑巴坦和头孢他啶-D 的转换为 667.2→199.3/139.0 和 551.9→467.9，他唑巴坦和舒巴坦的转换为 299.0→138/254.9 和 232.0→140.0。开发的测量程序用于指导骨关节炎感染患者的治疗和调整头孢洛扎他唑巴坦的日剂量。
在所有情况下，变异系数和绝对相对偏差均<7.9%和 6.5%。头孢洛扎他唑巴坦的定量下限、线性、归一化回收率、归一化基质效应和测量不确定度分别为：0.97mg/L，（0.97-125）mg/L，≤113.6%，≤108.7%和≤18.7%；他唑巴坦分别为 1.04mg/L、（1.04-125）mg/L、≤103.6%、≤101.9%和≤20.0%。未观察到干扰和交叉污染。患者的血浆浓度高于推荐的 3-4 倍最小抑菌浓度。
我们的测量程序适用于骨关节炎感染患者头孢洛扎他唑巴坦的治疗药物监测。
