Determination of nonsteroidal anti-inflammatory drugs in human tear and plasma samples using ultra-fast liquid chromatography-tandem mass spectrometry

To evaluate a new rapid and sensitive method for analyzing human tears and plasma for nonsteroidal anti-inflammatory drugs (NSAIDs) and investigate the influence of the transfer of NSAIDs in an ocular lesion. In this cross-over study, a single dose of 200 mg of ibuprofen and 60 mg of loxoprofen sodium were orally administered to six healthy Japanese subjects. Collected samples were analyzed by ultra-fast liquid chromatography tandem mass spectrometry (UFLC-MS/MS). Recoveries of the two drugs spiked in the tears and plasma were 96.0-117.0 % in the tears and 99.0-105.7 % in the plasma. Regression equations for both NSAIDs showed excellent linearity from 0.02-1.0 mu g/ml for the tears and 0.1-5.0 mu g/ml for the plasma, with the limits of detection at 0.02 mu g/ml for tears and 0.1 mu g/ml for plasma. This new high-throughput NSAID determination method only requires a small tear amount (10 mu l) and plasma volume (20 mu l) and thus will be useful in clinical and toxicological analyses. Analytical results also showed the presence of ibuprofen and loxoprofen in the actual tears and plasma, which confirms the transition of NSAIDs from the tears to the plasma.