Using a postcolumn-infused internal standard for correcting the matrix effects of urine specimens in liquid chromatography-electrospray ionization mass spectrometry

Hsiao Wei Liao, Guan Yuan Chen, I. Lin Tsai, Ching Hua Kuo

Research output: Contribution to journalArticle

18 Citations (Scopus)


Matrix effects (MEs) are a major problem affecting the quantitative accuracy of liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) when analyzing complicated samples. While analyzing urine specimens, the wide diversity of endogenous materials and different urine concentrations may result in inaccurate quantification. In this study, we propose a postcolumn-infused internal standard (PCI-IS) strategy for universal correction of MEs in urine specimens. MEs can be effectively corrected by dividing the target analyte signal intensity by the PCI-IS intensity. To evaluate the performance of PCI-IS, we used 6 benzodiazepine (BZD) drugs in 5 different concentrations of urine matrixes as a test model. The divergence of the BZD drug signal responses in 5 different urine matrixes was expressed using their respective coefficients of variation (CV) to evaluate the efficiency of using PCI-IS in correcting matrix effects. The CV of the BZD drug signal intensities in these 5 different concentrations of the urine matrixes were reduced from 10 to 30% to less than 10% when the PCI-IS correction method was employed. When the PCI-IS method was used to correct the 6 BZDs in 25 real human urine samples, over 90% of the test results exhibited quantification errors of less than 20%, and all of the test results had quantification errors of less than 30%. These results demonstrate that the PCI-IS method can resolve the problem of inaccurate quantification that arises from the diversity of urine specimens. The PCI-IS method is particularly useful for clinical analysis or forensic toxicology to improve the quantification accuracy in an economical way.

Original languageEnglish
Pages (from-to)97-104
Number of pages8
JournalJournal of Chromatography A
Publication statusPublished - Jan 31 2014
Externally publishedYes



  • Benzodiazepine (BZD)
  • Matrix effects
  • Postcolumn-infused internal standard (PCI-IS)
  • Urine concentrations

ASJC Scopus subject areas

  • Analytical Chemistry
  • Organic Chemistry
  • Biochemistry

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