Measuring concentrations of administered drugs and their metabolites in biological fluids, such as whole blood, plasma and serum, is important to understanding the efficacy and toxicological effects of the drugs. Typical clinical studies require handling and processing large numbers of biological fluid samples at low temperature with special care. Dried spot sampling is an alternative practice that is based on collection of small volumes (e.g., several microliters or less) of biological fluids as dried spots. For example, dried blood spot (DBS) sampling involves the collection of small volumes of blood onto a carrier medium typically in the form of a card. Samples are later reconstituted from the dried spots using a suitable solvent during an extraction process. The reconstituted samples can be analyzed, for example, in a liquid chromatography-mass spectrometry (LC-MS) assay.
Currently, a number of problems exist for DBS cards. For example, drug concentration can vary across samples according to the hematocrit of the subject and sampling of the entire spot is required to improve repeatability. In some applications, samples include analytes that are sensitive to light and humidity. Punching the DBS cards to remove the sample regions is typically performed with a punch tool that is repeatedly used so that carryover contamination can result. The lightweight discs released from the DBS card are difficult to handle and can limit the overall efficiency of a sample preparation extraction (SPE) workflow. Moreover, the act of punching the spots from the DBS card is tedious and can lead to repetitive strain injury.
In many instances, the analysis of reconstituted samples is adversely affected by the presence of interfering elements in the sample matrix. SPE is a chromatographic technique for preparing samples prior to performing quantitative analysis, for example, using high performance liquid chromatography (HPLC) or ultra performance liquid chromatography (UPLC). One goal of SPE is to isolate target analytes from a complex sample matrix containing unwanted interferences that can have a negative effect on the ability to perform quantitative analysis. The isolated target analytes are recovered in a solution that is compatible with quantitative analysis. The solution containing the target compound can be directly used for analysis. Alternatively, further processing can be performed, for example, by evaporation and reconstitution using another solution of a lesser volume to further concentrate the target compound for improved detection and measurement.
USPTO Backgrounds
USPTO Backgrounds