title: Measurement of ceftazidime concentration in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry. Application to critically ill patients and patients with osteoarticular infections.
abstract: Ceftazidime is an antibiotic belonging to the third generation of the cephalosporin family. It is indicated in the treatment of serious, simple or mixed bacterial infections, and its administration in continuous or intermittent infusion allows optimization of the concentration of antibiotic to keep it above the minimum inhibitory concentration. We developed and validated a chromatographic method by ultra-performance liquid chromatography-tandem mass spectrometry to measure ceftazidime concentration in human plasma. Following extraction with acetonitrile and 1,2-dichloroethane, the chromatographic separation was achieved using an Acquity ® UPLC ® BEH(TM) (2.1 × 100 mm i.d., 1.7 µm) reverse-phase C18 column, with a water-acetonitrile linear gradient containing 0.1% formic acid at a 0.4 mL/min flow rate. Ceftazidime and its internal standard (cefotaxime) were detected by electrospray ionization mass spectrometry in positive ion multiple reaction monitoring mode using mass-to-charge transitions of 547.0 → 467.9/396.1 and 456.0 → 395.8/324.1, respectively. The limit of quantification was 0.58 mg/L and linearity was observed in the range 0.58-160 mg/L. Coefficients of variation and absolute relative biases were <9.8 and 8.4%. The mean recovery for ceftazidime was 74.4 ± 8.1%. Evaluation of the matrix effect showed ion enhancement, and no carry-over was observed. The validated method could be applied to daily clinical laboratory practice to measure the concentration of ceftazidime in plasma.
authors.affiliation: Laboratori Clínic Department, IDIBELL, Hospital Universitari de Bellvitge,L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Raül
authors.initials: R
authors.lastname: Rigo-Bonnin
authors.affiliation: Pharmacy Department, IDIBELL, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Cobo-Sacristán
authors.affiliation: Pharmacy Department, IDIBELL, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Ariadna
authors.initials: A
authors.lastname: Padullés
authors.affiliation: Infectious Diseases, Orthopedic Surgery Department, IDIBELL, Hospital Universitari Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Ribera
authors.affiliation: Laboratori Clínic Department, IDIBELL, Hospital Universitari de Bellvitge,L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Ariadna
authors.initials: A
authors.lastname: Arbiol-Roca
authors.affiliation: Infectious Diseases, Orthopedic Surgery Department, IDIBELL, Hospital Universitari Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Murillo
authors.affiliation: Intensive Care Department, IDIBELL, Hospital Universitari Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Sabater-Riera
authors.affiliation: Laboratori Clínic Department, IDIBELL, Hospital Universitari de Bellvitge,L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Alía
mesh_terms: D001850:Bone Diseases, Infectious / Q000188:drug therapy*; D002442:Ceftazidime / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring; D004355:Drug Stability; D006801:Humans; D057230:Limit of Detection; D016014:Linear Models; D008826:Microbial Sensitivity Tests; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D002442:Ceftazidime
keywords: Pseudomonas aeruginosa; UPLC-MS/MS; cefotaxime; ceftazidime; minimal inhibitory concentration