Publisher's Synopsis
In the bioanalytical arena, gas-chromatography (GC) has long been established as the "gold standard" for the separation of small molecules. However, with the recent developments in LC-MS, this approach has become increasingly important for robust and reliable assays in the fields of clinical and forensic toxicology and doping control. LC has become an attractive alternative to GC, with the ability to analyse hydrophilic, thermolabile and non-volatile analytes, which were not sufficiently covered by GC. Additionally, LC-MS offers a fast, sensitive and selective approach where the simple sample preparation is amenable to fast, high-throughput assays and limits potential sources of error.
Apart from that, small, polar molecules present formidable challenges during LC-MS/MS analysis, such as (a) separation of metabolites from intended analyte, (b) analysis of thermally degradable drugs during ionisation, (c) separation of interfering/co-eluting peaks from the analyte and (d) elimination of the matrix effect. The above goals were resolved in order to avoid biased results for pharmacokinetics analysis.
The use of highly specific and sensitive analytical procedures is therefore required to achieve low limits of detection. The aim of this study was the development of sensitive and new analytical procedures for the accurate and specific determination of the selected drugs in human plasma, based on liquid chromatography-tandem mass spectrometry by overcoming above challenges.
The following drugs; Prasugrel active metabolite R-138727 (PAM), Triamcinolone acetonide (TRI), Ropinirole (ROP), Levodopa (LEV), Carbidopa (CAR) were selected to develop sensitive and reproducible LC-MS/MS bioanalytical methods for their estimation as individual or in combination in human plasma. The above selected drugs have unique challenges as mentioned above to develop highly sensitive and rugged methods. It would be useful for worldwide generic industry to expedite their regulatory filings.
