Abstract
Ceftriaxone is a cephalosporin antibiotic drug used as first-line treatment for several bacterial diseases. Ceftriaxone belongs to the third generation of antibiotics and is available as an intramuscular or intravenous injection. Previously published pharmacokinetic studies have mainly used high-performance liquid chromatography coupled with ultraviolet detection (HPLC-UV) for the quantification of ceftriaxone. This study aimed to develop and validate a bioanalytical method for the quantification of ceftriaxone in human plasma using liquid chromatography followed by tandem mass spectrometry (LC-MS/MS). Sample preparation was performed by protein precipitation in combination with phospholipid-removal techniques for cleaning up matrix interferences. The chromatographic separation was performed on an Agilent Zorbax Eclipse Plus C18 column with 10 mM ammonium formate containing 2% formic acid: acetonitrile as mobile phase at a flow rate of 0.4 ml/min. Both the analyte and cefotaxime (internal standard) were quantified using the positive electrospray ionization (ESI) mode and selected reaction monitoring (SRM) for the precursor-product ion transitions m/z 555.0→396.1 for ceftriaxone and 456.0→324.0 for cefotaxime. The method was validated over the concentration range of 1.01-200 μg/ml. Calibration response showed good linearity (correlation coefficient > 0.99) and no significant matrix effects were observed. The intra-assay and inter-assay precision were less than 5% and 10%, respectively, and therefore well within standard regulatory acceptance criterion of ±15%.
Highlights
Antibiotic resistance development is a serious global health concern
Development of widespread antibiotics resistance decreases the number of effective antibiotics rapidly, and new drug discovery does not demonstrate a healthy pipeline of novel drug to combat this rapidly increasing issue[5]
The calibration range of 1.01-200 μg/ml was based on pharmacokinetic data from previously published studies[6,8,17], taking into account the sensitivity and linearity of the MS instrument
Summary
Antibiotic resistance development is a serious global health concern. The number of deaths from drug-resistant infections is predicted to increase from 700,000 to 10 million deaths annually by 2050 with an estimated cost of up to US$ 100 trillion[1,2]. The impact of resistance will increase patient mortality, morbidity, length of hospitalization, and health-care costs[3,4]. Development of widespread antibiotics resistance decreases the number of effective antibiotics rapidly, and new drug discovery does not demonstrate a healthy pipeline of novel drug to combat this rapidly increasing issue[5]. Accurate and reliable bioanalytical methods for drug determination is a fundamental element to obtain reliable pharmacokinetic data
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