Effects of selected preanalytical variables on Dried Blood Spot (DBS) and Volumetric Adsorptive Microsampling (VAMS) based bioanalytical methods for the determination of four β-lactam antibiotics

Introduction: dose adjustment of antibiotic drugs is fundamental in critically ill patients and newborns, who may experience inadequate exposure of these drugs due to different pharmacokinetics (PK) and pharmacodynamics (PD) compared to other patients. Despite the increasing use of microsampling devices such as Dried Blood Spot (DBS) and Volumetric Absorptive Microsampling (VAMS) in paediatric clinical practice, little is reported on the comparison between these two devices in terms of β-lactam antibiotics quantification. Methods: a method using high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) for the simultaneous determination of amoxicillin, ampicillin, meropenem and cefadroxil from both DBS and VAMS has been evaluated. More specifically, we investigated the influence of some well-known critical pre-analytical parameters, such as blood haematocrit, blood spot volume and sample recovery approach on the results obtained with DBS-based and VAMS-based analytical methods. Results: our results show that comparable trueness and precision values can be achieved using both DBS- or VAMS-based methods. However, the latter was not affected by blood haematocrit value, whereas accuracy of the DBS-based approach was influenced by parameters as haematocrit, blood spot approaches (by pipette or hanging drop) and spot recovery procedures (DBS cut or punch). For the β-lactams tested, a significant longer stability was found for samples absorbed on DBS, when samples were stored at 4°C. Discussion: our data support the use of VAMS as preferable devices for β-lactam determinations, while more attention needs to be devoted to different pre-analytical variables for an accurate DBS quantification.