Development and validation of a serum total testosterone liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay calibrated to NIST SRM 971

Clin Chim Acta. 2013 Jan 16:415:109-17. doi: 10.1016/j.cca.2012.10.007. Epub 2012 Oct 16.

Abstract

Background: At our institution, serum testosterone in adult males is measured by immunoassay while female and pediatric specimens are sent to a reference laboratory for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis due to low concentrations. As this is of significant cost, a testosterone LC-MS/MS assay was developed in-house.

Methods: A 5500 QTRAP® using electrospray ionization and a Shimadzu Prominence with a C18 column were used. Gradient elution with formic acid, water and methanol:acetonitrile at 0.5 ml/min had a 7-min run-time. A liquid-liquid extraction with hexane:ethyl acetate was carried out on 200 μl of serum. Multiple reaction monitoring was employed.

Results: Sample preparation took ~80 min for 21 samples. Six calibrators were used (0-1263 ng/dl; concentration assigned by NIST SRM 971) with 3 quality controls (9, 168 and 532 ng/dl). The limits of detection and quantitation were 1 and 2 ng/dl respectively. Extraction recovery was ~90% and ion suppression ~5%. Within-run and total precision studies yielded <15% CV at the limit of quantitation and <7% CV through the rest of the linear range. Isobaric interferences were baseline separated from testosterone. Method comparisons between this assay, an immunoassay, and another LC-MS/MS assay were completed.

Conclusions: An accurate and sensitive LC-MS/MS assay for total testosterone was developed. Bringing this assay in-house reduces turnaround time for clinicians and patients and saves our institution funds.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biological Assay / standards*
  • Calibration
  • Child
  • Child, Preschool
  • Chromatography, Liquid / instrumentation
  • Chromatography, Liquid / methods
  • Chromatography, Liquid / standards*
  • Female
  • Humans
  • Limit of Detection
  • Male
  • Middle Aged
  • Observer Variation
  • Reference Standards
  • Reproducibility of Results
  • Tandem Mass Spectrometry / methods
  • Tandem Mass Spectrometry / standards*
  • Testosterone / blood*

Substances

  • Testosterone