Development of an UPLC–MS/MS method for the determination of antibiotic ertapenem on dried blood spots

Abstract

a b s t r a c tErtapenem (Invanz ® ) is a newly developed carbapenem ␤-lactam antimicrobial agent. The drug usage in pediatric age needs an accurate drug monitoring for effective patient management. The aim of this study was to evaluate the use of dried blood spot (DBS) specimens to measure ertapenem concentration during treatment. The analysis was performed by UPLC-MS/MS operating in multiple reaction monitoring (MRM) mode. The calibration curve in matrix was linear in the concentration range of 0.5-100 mg/L with correlation coefficient value higher than 0.997. Performance parameters of this method like lower limit of detection (LLOD, 0.2 mg/L), lower limit of quantification (LLOQ, 0.5 mg/L), matrix effect (20%), intra-and inter-day imprecision (CV within than 15%) and accuracy (between 94 and 155%) of drug concentrations have been evaluated. The drug stability at different temperatures was tested for one month, to evaluate the risks of sample delivery at different climatic conditions.The reported method allows now ertapenem analysis and offers many advantages for patients including the possibility of collecting samples at home.This new assay is both precise and accurate and is especially suitable for therapeutic drug monitoring and pharmacokinetic studies in neonates in whom obtaining larger blood samples is not convenient or possible.

Validation and Application of a Dried Blood Spot Assay for Biofilm-Active Antibiotics Commonly Used for Treatment of Prosthetic Implant Infections

“…Interface sources, electrospray ionization (ESI), and atmospheric pressure chemical ionization (APCI) were included in the system. All authentic standards (RIF, Des-RIF, FUS, and CIP) and internal standards (RIF-d 4 , Des-RIF-d 4 , CIP-d 8 , and FUS-d 6 ) were scanned for parent and product ions. The identified precursor and product ions of all drugs were further allowed to auto-optimize in the instrument.…”

“…Plasma was extracted by using a protein precipitation method. Plasma (20 l) was added to 50 l of EDTA and DFX solutions (stock, 2 g/liter) and precipitated by the addition of 300 l acetonitrile and methanol (50:50) containing the internal standards RIF-d 4 , Des-RIF-d 4 , FUS-d 6 , and CIP-d 8 . Samples were vortexed for 1 min and centrifuged at 1,500 ϫ g for 10 min.…”

“…Low-volume finger prick samples (10 to 20 l) are taken on filter paper, a method which could enable patients to collect their own samples in a domiciliary setting. Recent studies demonstrated that accurate measurement of drug concentrations in DBSs is feasible in animal models and human studies of antibiotics (5-7) and other drugs (8)(9)(10). Finger or heel prick samples can be taken serially and stored with a desiccant, without the need for processing and freezing of plasma.…”

“…Finger or heel prick samples can be taken serially and stored with a desiccant, without the need for processing and freezing of plasma. A small-diameter disc, or chad, can be subsequently punched out from the filter paper, and the drug can be eluted into a liquid matrix prior to a liquid chromatography-mass spectrometry (LC-MS) assay (6,8,10). However, there are few studies that have demonstrated that DBS drug concentrations can be applied in PK/PD studies as reliable surrogates for plasma concentrations.…”

Role of Therapeutic Drug Monitoring in Pulmonary Infections: Use and Potential for Expanded Use of Dried Blood Spot Samples

“…interactions [36,[70][71][72][73]. Voriconazole has a nonlinear pharmacokinetic profile and there is a wide 418 intra and interindividual variety [71].…”