Direct in situ labeling of target drugs with a fluorophore probe to improve MALDI-MS detection sensitivity in micro-liter plasma

摘要

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for symptomatic relief from fever, inflammation, and chronic pain associated with a variety of human disorders. Long-term usage of these drugs can result in severe syndromes; hence, their dose should be controlled carefully and their side effects such as Stevens–Johnson syndrome, toxic epidermal necrolysis, phototoxicity, acute interstitial nephritis, gastrointestinal bleeding, cardiovascular diseases, and liver injury should be considered. Furthermore, the widely used combination of NSAIDs as over-the-counter (OTC) drugs with other drugs leads to adverse drug–drug interactions. Therefore, development of a throughput method to rapidly screen 20 NSAIDs in biological samples is necessary to safeguard human health. In this work, we selected a suitable fluorophore probe coupled with in situ micro-labeling (<2 min) on stainless plate for the fast detection of NSAIDs in plasma samples at the micro-liter level (5 μL) without complicated sample preparation and separation. Every step undertaken in the protocol was also at the micro-liter level; thus, a small amount of blood collected from the human finger will suffice to determine the drug concentration in blood using the proposed method. Furthermore, the proposed method we developed was also matched the modern trends of green analytical chemistry towards miniaturization of analytical methodologies.