title: Rapid, accurate and precise quantitative drug analysis: comparing liquid chromatography tandem mass spectrometry and chip-based nanoelectrospray ionisation mass spectrometry.
abstract: We have developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) system capable of achieving better than 2% accuracy, routinely over a wide concentration range of 1800 ng mL-1. We demonstrate that the necessary high precision, high accuracy and rapid analysis can be achieved using LC-MS/MS technology. Automated nanoelectrospray ionisation tandem mass spectrometry (nanoESI-MS/MS) technology can be employed to eliminate the chromatographic step completely. In this paper, nanoESI-MS/MS is evaluated and compared directly with LC-MS/MS for the quantitative analysis of two-test analytes, amitriptyline (ATT) and 5-methoxytryptamine (5-MTT), in aqueous/organic mixture. Calibration curves were found to be linear over a wide concentration range of 1800 ng mL-1 for both analytes using LC-MS/MS. Using nanoESI-MS/MS ATT gave a linear response while 5-MTT gave a non-linear response using nanoESI-MS/MS over the same concentration range as in LC-MS/MS. Accuracy and precision values of quality control samples (QCs) at four concentration levels were analysed in replicates of six at each level using 5-MTT and ATT as test analytes for both techniques. The LC-MS/MS system was capable of achieving accuracy levels of 99.50101.96% for ATT and 100.17100.40% for 5-MTT. Accuracy levels using nanoESI-MS/MS were not comparable to LC-MS/MS, they ranged from 90.09100.18% for ATT and 95.95113.55% for 5-MTT. The precision values obtained for nanoESI-MS/MS were in good agreement with those obtained by LC-MS/MS.
authors.affiliation: Medway Science, University of Greenwich, Medway Camps, Chatham, Kent ME4 4TB, UK.
authors.forename: Louisa N
authors.initials: LN
authors.lastname: Alfazema
authors.forename: Don S
authors.initials: DS
authors.lastname: Richards
authors.forename: Sylvie
authors.initials: S
authors.lastname: Gélébart
authors.forename: John C
authors.initials: JC
authors.lastname: Mitchell
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Snowden
mesh_terms: D008735:5-Methoxytryptamine / Q000032:analysis*; D000639:Amitriptyline / Q000032:analysis*; D018712:Analgesics, Non-Narcotic / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D008832:Microchemistry; D046208:Microchip Analytical Procedures / Q000379:methods*; D036103:Nanotechnology; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D018712:Analgesics, Non-Narcotic; D000639:Amitriptyline; D008735:5-Methoxytryptamine