An Ultra-High-Performance Liquid Chromatography–Tandem Mass Spectrometry Method for Simultaneous Determination of 4 β-Lactam Antibiotics, Tazobactam, and Linezolid in Human Plasma Samples

Abstract

Background: Optimization of antimicrobial therapy is a challenge in critically ill patients who develop extreme interindividual and intraindividual pharmacokinetic variability. Therapeutic drug monitoring is a valuable tool for maximizing the effect of a drug and minimizing its adverse and unwanted effects. The aim of the current work was to develop and validate an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to determine multiple antibiotics in clinical plasma samples from critically ill patients; low sample volume and rapid processing of samples were considered the main criteria.Methods: A separation method based on an online combination of UHPLC-MS/MS was developed for the simultaneous determination of 4 b-lactam antibiotics (cefepime, meropenem, cefotaxime, and piperacillin), tazobactam, and linezolid in human plasma samples. The volume of plasma sample used for analysis was 20 mL. The developed method was validated according to Food and Drug Administration guidelines. Results:The chromatographic run time was 8 minutes. Calibration curves were linear for concentration ranges of 0.1-100 mcg/mL (r 2 . 0.99) for tazobactam, meropenem, cefotaxime, linezolid, and piperacillin and 1-100 mcg/mL (r 2 . 0.99) for cefepime. The intraday and interday accuracy of the method ranged from 92.4% to 110.7% and 93.6% to 113.3%, respectively. The intraday and interday pre-cision values were #17.3% and #17.4%, respectively. No interfering and carryover analytes were observed. Conclusions:The developed UHPLC-MS/MS method is an appropriate and practical tool for therapeutic drug monitoring of the selected antibiotics. Owing to its rapidity, requirement of low sample volume, and high selectivity, sensitivity, and reliability, it can be effectively implemented in routine clinical laboratory tests for critically ill patients.

Development and Validation of a Capillary Zone Electrophoresis–Tandem Mass Spectrometry Method for Simultaneous Quantification of Eight β-Lactam Antibiotics and Two β-Lactamase Inhibitors in Plasma Samples

“…The following m / z ion quantification transitions were applied in the MRM mode for each investigated analyte: AMX 366.1 → 113.7, AMP 350.0 → 106.1, CTX 456 →166.7, CAZ 547.1 → 395.8, FLX 454.1 → 295, MER 384.0 → 113.7, OXA 402.1 → 160.0, PIP 518.0 → 143.0, SUL 234.0 → 123.8, and TAZ 301.1 → 168. These transitions were in good agreement with previously published data [ 1 , 22 , 24 , 51 ]. Details regarding quantitation and identity confirmation transitions for the investigated β-lactam ATBs, inhibitors of β-lactamase, and their associated internal standards are summarized in Table 2 .…”

“…There are no immunoassays available for β-lactam ATBs quantification. Liquid chromatography (LC) methods coupled with ultraviolet (UV) [ 16 , 17 , 18 , 19 , 20 ] or mass spectrometry (MS) detection [ 1 , 21 , 22 , 23 , 24 ] are primarily utilized for this purpose. However, a TLC method was also developed for this purpose [ 25 ].…”

Development and Validation of UFLC-MS/MS Analytical Method for the Simultaneous Quantification of Antibiotic Residues in Surface Water, Groundwater, and Pharmaceutical Waste Water Samples from South India

“…16 Antibiotic risk assessments for humans have been studied in the UK, Australia, and the US, where the minimal therapeutic dose, or lowest active drug concentration, of an antibiotic in drinking water is typically more than a thousand times lower (WHO, 2011). 17 One of the largest challenges to world health is antibiotic resistance, which can afflict people of any age in any nation and raise hospital stays, death rates, and related expenses. Pharmaceutical industry is feeling the rise of superbugs through pollution in its supply chains.…”

“…When it comes to antibiotics, comprehensive preclinical and clinical testing are necessary to ascertain their viability prior to commercialization, as long as they are categorized as environmental pollutants . Antibiotic risk assessments for humans have been studied in the UK, Australia, and the US, where the minimal therapeutic dose, or lowest active drug concentration, of an antibiotic in drinking water is typically more than a thousand times lower (WHO, 2011) …”

“… 16 Antibiotic risk assessments for humans have been studied in the UK, Australia, and the US, where the minimal therapeutic dose, or lowest active drug concentration, of an antibiotic in drinking water is typically more than a thousand times lower (WHO, 2011). 17 …”