Implementation of high-temperature superficially porous technologies for rapid LC-MS/MS diastereomer bioanalysis

Bioanalysis. 2011 Apr;3(7):735-43. doi: 10.4155/bio.11.17.

Abstract

Background: The fast-paced nature of the pharmaceutical industry requires robust bioanalytical methods to endure the high-throughput sample demands of the production environment.

Results: A rapid, accurate and precise LC-MS/MS method was developed for the quantitation of a diastereomer quartet in human plasma. Virtually all of the phosphatidylcholine and most of the lysophosphatidylcholine from human plasma were removed using a phospholipid-removing protein precipitation 96-well plate. An Agilent Poroshell SB-C18 2.1 × 50 mm superficially porous column was used at 100°C and 1.2 ml/min to separate a diastereomer quartet in <2.5 min. Peak shape, retention and resolution were maintained over nearly 200 extracted bioanalytical samples under these separation conditions. The method was tested for accuracy and precision; the assay inter-run accuracy and precision were minus 7.2-0.7% and 2.1-11.9%, respectively (n = 18).

Conclusion: The application of the superficially porous column resulted in twofold response increase and a 2.6-fold reduction in cycle time compared with a 3.5-µm column performing under comparable resolution conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Chemical Analysis / instrumentation*
  • Blood Chemical Analysis / methods
  • Chromatography, High Pressure Liquid / instrumentation*
  • Chromatography, High Pressure Liquid / methods
  • Cyclopropanes
  • Dipeptides / blood*
  • Humans
  • Leucine / analogs & derivatives
  • Lysophosphatidylcholines / blood
  • Phosphatidylcholines / blood
  • Proline / analogs & derivatives
  • Stereoisomerism
  • Sulfones / blood*
  • Tandem Mass Spectrometry / instrumentation*
  • Tandem Mass Spectrometry / methods
  • Technology, Pharmaceutical / instrumentation*
  • Technology, Pharmaceutical / methods
  • Temperature
  • Urea

Substances

  • Cyclopropanes
  • Dipeptides
  • Lysophosphatidylcholines
  • Phosphatidylcholines
  • Sulfones
  • narlaprevir
  • Urea
  • Proline
  • Leucine