Automated Extraction and Quantification of Immunosuppressants and Anticonvulsants from Dried Blood Spots: Evaluation of Transcend DBSA–TLX-1–MS/MS System
Pragya Sharma, Alison Lightfoot, Richard G. Lahr, Chris Thompson, Jennifer Faber, Joshua Miller, Jingshu Guo, Loralie J. Langman, Paul J. Jannetto, Anthony Maus
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引用次数: 0
Abstract
Immunosuppressants and anticonvulsant drugs are routinely quantified using liquid chromatography–tandem mass spectrometry (LC–MS/MS) in whole blood and serum, respectively, which necessitates frequent phlebotomy visits for patients. Alternatively, dried blood spots (DBS) measurements have the potential to reduce the cost of sample collection and shipping, while simultaneously enabling convenient at-home collection for patients. We evaluated Transcend™ DBSA–TLX-1–MS/MS System through method development and analytical validation for measurements of immunosuppressants (tacrolimus, sirolimus and everolimus) and anticonvulsants (levetiracetam and lamotrigine) in DBS. Given the relatively low analytical measurement interval (AMI) for these immunosuppressants, sufficient sensitivity is imperative, and the desired lower limit of quantitation (LLOQ) of 1 ng/mL was achieved, with an interday %CV less than 10% at the LLOQ. Conversely, the comparatively high AMI for the anticonvulsant drugs necessitated careful optimization to avoid saturation and minimize imprecision. For all analytes, carryover was minimal, and linearity and accuracy using spiked samples indicated adequate performance based on the regression comparisons. Therefore, our proof-of-concept study suggests that the DBSA–TLX-1–MS/MS has the potential to provide exceptional analytical performance, which will facilitate future clinical validations while minimizing labor required to perform DBS measurements.
期刊介绍:
Separation sciences, in all their various forms such as chromatography, field-flow fractionation, and electrophoresis, provide some of the most powerful techniques in analytical chemistry and are applied within a number of important application areas, including archaeology, biotechnology, clinical, environmental, food, medical, petroleum, pharmaceutical, polymer and biopolymer research. Beyond serving analytical purposes, separation techniques are also used for preparative and process-scale applications. The scope and power of separation sciences is significantly extended by combination with spectroscopic detection methods (e.g., laser-based approaches, nuclear-magnetic resonance, Raman, chemiluminescence) and particularly, mass spectrometry, to create hyphenated techniques. In addition to exciting new developments in chromatography, such as ultra high-pressure systems, multidimensional separations, and high-temperature approaches, there have also been great advances in hybrid methods combining chromatography and electro-based separations, especially on the micro- and nanoscale. Integrated biological procedures (e.g., enzymatic, immunological, receptor-based assays) can also be part of the overall analytical process.