Addressing the challenge of limited sample volumes in in vitro studies with capillary-scale microfluidic LC-MS/MS

Miniaturization of chromatographic separation systems provides a means of greatly increasing sensitivity in LC–MS. In this article, we demonstrate the use of an integrated microfluidic chromatographic device for the LC–MS/MS investigation of the in vitro microsomal metabolism of the model drug propranolol using a sample volume of 1 μl of a 1-μM incubation. With such samples the system was capable of obtaining high-quality MS and MS/MS data from the injection of test drug substance containing sufficient information to correctly derive the structure of the drug metabolites. The analytical column was tolerant to the injection of a large percentage of organic...