Dried blood spot sampling in combination with LC‐MS/MS for quantitative analysis of small molecules

Abstract

The collection of whole blood samples on paper, known as dried blood spot (DBS), dates back to the early 1960s in newborn screening for inherited metabolic disorders. DBS off ers a number of advantages over conventional blood collection. As a less invasive sampling method, DBS off ers simpler sample collection and storage and easier transfer, with reduced infection risk of various pathogens, and requires a smaller blood volume. To date, DBS-LC-MS/MS has emerged as an important method for quantitative analysis of small molecules. Despite the increasing popularity of DBS-LC-MS/MS, the method has its limitations in assay sensitivity due to the small sample size. Sample quality is often a concern. Systematic assessment on the potential impact of various blood sample properties on accurate quantifi cation of analyte of interest is necessary. Whereas most analytes may be stable on DBS, unstable compounds present another challenge for DBS as enzyme inhibitors cannot be conveniently mixed during sample collection. Improvements on the chemistry of DBS card are desirable. In addition to capturing many representative DBS-LS-MS/MS applications, this review highlights some important aspects of developing and validating a rugged DBS-LC-MS/MS method for quantitative analysis of small molecules along with DBS sample collection, processing and storage.

Therapeutic drug monitoring of carbamazepine and its metabolite in children from dried blood spots using liquid chromatography and tandem mass spectrometry

“…In order to implement the use of DBS in clinical practice, a comparison between DBS and plasma concentrations is required since DBS concentrations are not equal to plasma concentrations [30,31].…”

A validated method for the quantification of fosfomycin on dried plasma spots by HPLC–MS/MS: Application to a pilot pharmacokinetic study in humans

“…The validation was performed in accordance with the guidelines provided by the US FDA with pre-established acceptance criteria required to demonstrate the method is suitable for the intended purpose [30] and current scientific standards on microsampling [31][32][33]. The validation for extraction of fosfomycin from dried plasma spots was assessed for lower limit of quantification (LLOQ), linearity, inter-day precision and accuracy, sample spot volume, matrix effects, recovery, storage and transport stability.…”

Rapid and sensitive LC–MS/MS method for the analysis of antibiotic linezolid on dried blood spot

“…This fact is due to the low spotted blood volume on paper (20 L) generating an homogenous spot [15,16].…”