Ampiroxicam

A high-performance liquid chromatography-tandem mass spectrometry (LC/MS/MS) technique was developed for the simultaneous determination of five non-steroidal anti-inflammatory oxicam drugs (ampiroxicam, tenoxicam, piroxicam, meloxicam and lornoxicam) in human plasma. These five oxicam drugs and isoxicam (internal standard) were extracted from human plasma with an Oasis(®) MAX cartridge column and analysed on a Unison UK-C18 column (2.0 mm × 100 mm, 3 μm) with an acetonitrile:10mM formic ammonium buffer (pH 3.0) (50:50) mobile phase at 0.20 ml/min at 37°C. The analytes were detected using a tandem mass spectrometer, equipped with an electrospray ion source (ESI). The instrument was used in multiple-reaction-monitoring (MRM) mode. The extraction yields from a 200 μl human plasma sample (containing 10 ng of each drugs) with the Oasis(®) MAX cartridge column were 93.3-102.5%. The detection limits were 0.01-6.5 ng/ml (S/N=3). Our developed method is very useful for the simultaneous determination of five oxicam (non-steroidal anti-inflammatory) drugs in human plasma by LC/MS/MS.

In the treatment of Parkinson's disease, potent disease-modifying drugs are still needed to halt progressive dopaminergic neurodegeneration. We have previously shown that meloxicam, an oxicam non-steroidal anti-inflammatory drug (NSAID), elicits a potent neuroprotective effect against 1-methyl-4-phenyl pyridinium (MPP(+))-induced toxicity in human dopaminergic SH-SY5Y neuroblastoma cells. This cyclooxygenase-independent neuroprotection of meloxicam is mediated via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway; however, the specific chemical structure involved in inducing neuroprotection remains unresolved. In this study, we therefore investigated the structure-specific for eliciting the neuroprotective effect by examining a series of NSAIDs against MPP(+) toxicity in SH-SY5Y cells. Three oxicam-bearing NSAIDs showed potent neuroprotective effects, although none of the other 10 oxicam-nonbearing NSAIDs (3 salicylates, 6 coxibs and 1 polyphenol) or 3 piroxicam analogs (including ampiroxicam, a precursor of piroxicam) exerted any neuroprotection. Tenoxicam and piroxicam prevented MPP(+)-induced reduction of phosphorylated Akt levels in cells: a protective mechanism similar to that of meloxicam. Therefore, the oxicam structure was likely to be responsible for exhibiting the neuroprotection by sustaining survival-signaling in dopaminergic cells. The present results raise the possibility that the oxicam-bearing NSAIDs may serve as potential therapeutic drugs to retard or terminate progression of Parkinson's disease via a novel mechanism.