Journal: Journal of Mass Spectrometry and Advances in the Clinical Lab

Article Title: LC–MS/MS method for simultaneous quantification of ten antibiotics in human plasma for routine therapeutic drug monitoring

doi: 10.1016/j.jmsacl.2022.11.001

Figure Lengend Snippet: Mass spectrometry fragmentation pattern for cefazolin (CZO), cefepime (CEP), cefotaxime (CTA), ceftazidime (CTZ), ciprofloxacin (CIP), flucloxacillin (FLU), linezolid (LIN), meropenem (MER), piperacillin (PIP) and tazobactam (TAZ).

Article Snippet: Cefazolin sodium (98 % purity), cefazolin 13 C 2 15 N (CZO-IS; 98.6 % isotopic purity), cefepime dihydrochloride monohydrate (98 % purity), cefepime 2 H 3 sulfate (CEP-IS; 98.6 % isotopic purity), cefotaxime 2 H 3 (CTA-IS; 99.8 % isotopic purity), ceftazidime pentahydrate (97 % purity), ceftazidime 2 H 5 (CTZ-IS; 99.4 % isotopic purity), ciprofloxacin (98 % purity), ciprofloxacin 2 H 8 (CIP-IS; 98.3 % isotopic purity), flucloxacillin sodium (97 % purity), flucloxacillin 13 C 4 (FLU-IS; 99.5 % isotopic purity), linezolid (98 % purity), linezolid 2 H 3 (LIN-IS; 98.3 % isotopic purity), meropenem trihydrate (97 % purity), meropenem 2 H 6 (MER-IS; 99.6 % isotopic purity), piperacillin 2 H 5 (PIP-IS; 98.9 % isotopic purity), tazobactam sodium (96 % purity), tazobactam sodium 13 C 2 15 N (TAZ-IS; 97.9 % isotopic purity) were purchased from Toronto Research Chemicals (PM Separations, Australia).

Techniques: Mass Spectrometry

Journal: Journal of Mass Spectrometry and Advances in the Clinical Lab

Article Title: LC–MS/MS method for simultaneous quantification of ten antibiotics in human plasma for routine therapeutic drug monitoring

doi: 10.1016/j.jmsacl.2022.11.001

Figure Lengend Snippet: Chromatograms for cefepime (CEP, 1), tazobactam (TAZ, 2), ceftazidime (CTZ, 3), meropenem (MER, 4), ciprofloxacin (CIP, 5), cefotaxime (CTA, 6), cefazolin (CZO, 7), linezolid (LIN, 8), piperacillin (PIP, 9) and flucloxacillin (FLU, 10) in human plasma at lower limit of quantitation.

Article Snippet: Cefazolin sodium (98 % purity), cefazolin 13 C 2 15 N (CZO-IS; 98.6 % isotopic purity), cefepime dihydrochloride monohydrate (98 % purity), cefepime 2 H 3 sulfate (CEP-IS; 98.6 % isotopic purity), cefotaxime 2 H 3 (CTA-IS; 99.8 % isotopic purity), ceftazidime pentahydrate (97 % purity), ceftazidime 2 H 5 (CTZ-IS; 99.4 % isotopic purity), ciprofloxacin (98 % purity), ciprofloxacin 2 H 8 (CIP-IS; 98.3 % isotopic purity), flucloxacillin sodium (97 % purity), flucloxacillin 13 C 4 (FLU-IS; 99.5 % isotopic purity), linezolid (98 % purity), linezolid 2 H 3 (LIN-IS; 98.3 % isotopic purity), meropenem trihydrate (97 % purity), meropenem 2 H 6 (MER-IS; 99.6 % isotopic purity), piperacillin 2 H 5 (PIP-IS; 98.9 % isotopic purity), tazobactam sodium (96 % purity), tazobactam sodium 13 C 2 15 N (TAZ-IS; 97.9 % isotopic purity) were purchased from Toronto Research Chemicals (PM Separations, Australia).

Techniques: Clinical Proteomics, Quantitation Assay

Journal: Journal of Mass Spectrometry and Advances in the Clinical Lab

Article Title: LC–MS/MS method for simultaneous quantification of ten antibiotics in human plasma for routine therapeutic drug monitoring

doi: 10.1016/j.jmsacl.2022.11.001

Figure Lengend Snippet: Intra and inter-day precision and accuracy data.

Article Snippet: Cefazolin sodium (98 % purity), cefazolin 13 C 2 15 N (CZO-IS; 98.6 % isotopic purity), cefepime dihydrochloride monohydrate (98 % purity), cefepime 2 H 3 sulfate (CEP-IS; 98.6 % isotopic purity), cefotaxime 2 H 3 (CTA-IS; 99.8 % isotopic purity), ceftazidime pentahydrate (97 % purity), ceftazidime 2 H 5 (CTZ-IS; 99.4 % isotopic purity), ciprofloxacin (98 % purity), ciprofloxacin 2 H 8 (CIP-IS; 98.3 % isotopic purity), flucloxacillin sodium (97 % purity), flucloxacillin 13 C 4 (FLU-IS; 99.5 % isotopic purity), linezolid (98 % purity), linezolid 2 H 3 (LIN-IS; 98.3 % isotopic purity), meropenem trihydrate (97 % purity), meropenem 2 H 6 (MER-IS; 99.6 % isotopic purity), piperacillin 2 H 5 (PIP-IS; 98.9 % isotopic purity), tazobactam sodium (96 % purity), tazobactam sodium 13 C 2 15 N (TAZ-IS; 97.9 % isotopic purity) were purchased from Toronto Research Chemicals (PM Separations, Australia).

Techniques: Concentration Assay

Journal: Journal of Mass Spectrometry and Advances in the Clinical Lab

Article Title: LC–MS/MS method for simultaneous quantification of ten antibiotics in human plasma for routine therapeutic drug monitoring

doi: 10.1016/j.jmsacl.2022.11.001

Figure Lengend Snippet: Recovery (%) of the spiked patient samples (n = 35). Samples from patients requested for antimicrobial monitoring were analyzed in duplicate: a) neat and b) spiked with a solution mixture containing all the analytes. The recovered concentrations were calculated by subtracting the concentration obtained for the neat sample from the spiked (b-a). The percent recovery (%) was calculated from recovered concentration divided by the concentration of the spiked solution mixture and multiplied by 100. The recovery (%) was withing 85–115 %, except for CEP (81–124 %). CZO, cefazolin; CEP, cefepime; CTA, cefotaxime; CTZ, ceftazidime; CIP, ciprofloxacin; FLU, flucloxacillin; LIN, linezolid; MER, meropenem; PIP, piperacillin; TAZ, tazobactam.

Article Snippet: Cefazolin sodium (98 % purity), cefazolin 13 C 2 15 N (CZO-IS; 98.6 % isotopic purity), cefepime dihydrochloride monohydrate (98 % purity), cefepime 2 H 3 sulfate (CEP-IS; 98.6 % isotopic purity), cefotaxime 2 H 3 (CTA-IS; 99.8 % isotopic purity), ceftazidime pentahydrate (97 % purity), ceftazidime 2 H 5 (CTZ-IS; 99.4 % isotopic purity), ciprofloxacin (98 % purity), ciprofloxacin 2 H 8 (CIP-IS; 98.3 % isotopic purity), flucloxacillin sodium (97 % purity), flucloxacillin 13 C 4 (FLU-IS; 99.5 % isotopic purity), linezolid (98 % purity), linezolid 2 H 3 (LIN-IS; 98.3 % isotopic purity), meropenem trihydrate (97 % purity), meropenem 2 H 6 (MER-IS; 99.6 % isotopic purity), piperacillin 2 H 5 (PIP-IS; 98.9 % isotopic purity), tazobactam sodium (96 % purity), tazobactam sodium 13 C 2 15 N (TAZ-IS; 97.9 % isotopic purity) were purchased from Toronto Research Chemicals (PM Separations, Australia).

Techniques: Concentration Assay

Journal: Journal of Mass Spectrometry and Advances in the Clinical Lab

Article Title: LC–MS/MS method for simultaneous quantification of ten antibiotics in human plasma for routine therapeutic drug monitoring

doi: 10.1016/j.jmsacl.2022.11.001

Figure Lengend Snippet: Summary of the stability data for all analytes in plasma and whole blood matrices. The stability of the analyte is assumed for the length of time at the specified temperature.

Article Snippet: Cefazolin sodium (98 % purity), cefazolin 13 C 2 15 N (CZO-IS; 98.6 % isotopic purity), cefepime dihydrochloride monohydrate (98 % purity), cefepime 2 H 3 sulfate (CEP-IS; 98.6 % isotopic purity), cefotaxime 2 H 3 (CTA-IS; 99.8 % isotopic purity), ceftazidime pentahydrate (97 % purity), ceftazidime 2 H 5 (CTZ-IS; 99.4 % isotopic purity), ciprofloxacin (98 % purity), ciprofloxacin 2 H 8 (CIP-IS; 98.3 % isotopic purity), flucloxacillin sodium (97 % purity), flucloxacillin 13 C 4 (FLU-IS; 99.5 % isotopic purity), linezolid (98 % purity), linezolid 2 H 3 (LIN-IS; 98.3 % isotopic purity), meropenem trihydrate (97 % purity), meropenem 2 H 6 (MER-IS; 99.6 % isotopic purity), piperacillin 2 H 5 (PIP-IS; 98.9 % isotopic purity), tazobactam sodium (96 % purity), tazobactam sodium 13 C 2 15 N (TAZ-IS; 97.9 % isotopic purity) were purchased from Toronto Research Chemicals (PM Separations, Australia).

Techniques: Clinical Proteomics

Journal: Journal of Mass Spectrometry and Advances in the Clinical Lab

Article Title: LC–MS/MS method for simultaneous quantification of ten antibiotics in human plasma for routine therapeutic drug monitoring

doi: 10.1016/j.jmsacl.2022.11.001

Figure Lengend Snippet: Antimicrobials concentrations of patients requested for therapeutic drug monitoring. MIC breakpoints for each agent were set based on the EUCAST PK/PD clinical breakpoints and are non-species related. The breakpoints for the susceptible (S) and resistant (R) organisms were 4 and 8 mg/L (CEP, CTZ); 1 and 2 mg/L (CZO, CTA); 0.25 and 0.5 mg/L (CIP); 2 and 4 (FLU); 2 and 8 mg/L (MER); 2 and 2 mg/L (LIN) and 8 and 16 mg/L (PIP), respectively. The target plasma concentration ranges set as 4 and 8 times the MIC breakpoint of the R organism were as per recommendation of the French Society of Pharmacology and Therapeutics (SFPT) and the French Society of Anesthesia and Intensive Care Medicine (SFAR) . The targets of the total drug concentrations for CZO, CEP, CTA, CTZ, PIP and FLU, were based on the free drug fraction (%) and the MIC of the pathogen. For CZO, for example, the target free plasma concentration of 4 to 8 times the MIC of R (2 mg/L) is 8 and 16 mg/L, respectively. As the free fraction of CZO is approximately 20 % of the total dose, the target total plasma concentration is 40–80 mg/L. The estimated free fraction (%) for CZO, CEP, CTA, CTZ, PIP and FLU were approximately 15–20, 80, 60–80, 90, 80 and 5–10 %, respectively. For CEP, the target plasma concentration (5–35 mg/L) were taken from the SEPT and SFAR guidelines where calculations were based on the MIC of 1 mg/L ( Enterobacteriaceae ) and not 8 mg/L ( P. aeruginosa ), since this would have resulted in a concentration above the defined toxic threshold. For CTA and MER, the target ranges were also from the SEPT and SFAR guidelines and were based on the MIC of 4 mg/L for S. aureus and 2 mg/L for P. aeruginosa , respectively. For LIN and FLU, the targets were based on the 2–4 times the MIC . For CIP, the target range was set as Cmax/MIC > 10. TAZ range was 2–5 mg/L at 500 mg given with PIP. MIC, minimum inhibitory concentration; EUCAST, European Committee on Antimicrobial Susceptibility Testing; PK/PD, pharmacokinetic/pharmacodynamic; Cmax, maximum concentration; CZO, cefazolin; CEP, cefepime; CTA, cefotaxime; CTZ, ceftazidime; CIP, ciprofloxacin; FLU, flucloxacillin; MER, meropenem; LIN, linezolid; PIP, piperacillin; TAZ, tazobactam; S, susceptible, wild-type organism; R, resistant organism.

Article Snippet: Cefazolin sodium (98 % purity), cefazolin 13 C 2 15 N (CZO-IS; 98.6 % isotopic purity), cefepime dihydrochloride monohydrate (98 % purity), cefepime 2 H 3 sulfate (CEP-IS; 98.6 % isotopic purity), cefotaxime 2 H 3 (CTA-IS; 99.8 % isotopic purity), ceftazidime pentahydrate (97 % purity), ceftazidime 2 H 5 (CTZ-IS; 99.4 % isotopic purity), ciprofloxacin (98 % purity), ciprofloxacin 2 H 8 (CIP-IS; 98.3 % isotopic purity), flucloxacillin sodium (97 % purity), flucloxacillin 13 C 4 (FLU-IS; 99.5 % isotopic purity), linezolid (98 % purity), linezolid 2 H 3 (LIN-IS; 98.3 % isotopic purity), meropenem trihydrate (97 % purity), meropenem 2 H 6 (MER-IS; 99.6 % isotopic purity), piperacillin 2 H 5 (PIP-IS; 98.9 % isotopic purity), tazobactam sodium (96 % purity), tazobactam sodium 13 C 2 15 N (TAZ-IS; 97.9 % isotopic purity) were purchased from Toronto Research Chemicals (PM Separations, Australia).

Techniques: Clinical Proteomics, Concentration Assay