Rapid, accurate and precise quantitative drug analysis: comparing liquid chromatography tandem mass spectrometry and chip-based nanoelectrospray ionisation mass spectrometry

Eur. J. Mass Spectrom. 11, 393–402 (2005)
DOI: 10.1255/ejms.772

Rapid, accurate and precise quantitative drug analysis: comparing liquid chromatography tandem mass spectrometry and chip-based nanoelectrospray ionisation mass spectrometry

Louisa N. Alfazema,^a,b,* Don S. Richards,^b Sylvie Gélébart,^b John C. Mitchell,^a Martin J. Snowden^a
^aMedway Science, University of Greenwich, Medway Camps, Chatham, Kent ME4 4TB, UK
^bAnalytical R and D, Pfizer Global Research & Development, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK

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 1–800 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 1–800 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 99.50–101.96% for ATT and 100.17–100.40% for 5-MTT. Accuracy levels using nanoESI-MS/MS were not comparable to LC-MS/MS, they ranged from 90.09–100.18% for ATT and 95.95–113.55% for 5-MTT. The precision values obtained for nanoESI-MS/MS were in good agreement with those obtained by LC-MS/MS.

Keywords: accuracy. precision, 5-methoxytryptamine, amitriptyline, quantitative MS/MS, chip-based nanoelectrospray

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