Variability of the IS revealed ionization enhancement by bile acid in mouse plasma.
BACKGROUND
Elevated IS response was observed in 22 out of 157 mouse plasma samples in a 3-month toxicity study. This initiated a root cause investigation.


RESULTS
Mass spectra revealed that taurocholic acid (TCA) was present in the samples, partially eluted overlapping the analyte peak. An enhanced IS response (> twofold) was reproduced by injecting TCA together with the IS. Tests with five other drug compounds showed compound dependent matrix effects on ESI; enhancement as well as suppression. The matrix effects did not affect the integrity of study results, most likely due to the use of a 13C-labeled IS.


CONCLUSIONS
The variability of TCA levels in plasma as well as the observed instability of the chromatographic retention complicates the evaluation of TCA-induced matrix effects during method development. Thus, monitoring the IS response in incurred samples is a useful tool to evaluate the performance of a validated method.
AstraZeneca R&D, Pepparedsleden 1, Mölndal, SE-43183, Sweden.
Anders O
AO
Olsson
Maria
M
Jelvestam
Martin
M
Ahnoff
D000818:Animals; D002247:Carbon Isotopes / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D007477:Ions / Q000737:chemistry; D007553:Isotope Labeling; D051379:Mice; D004364:Pharmaceutical Preparations / Q000032:analysis; D021241:Spectrometry, Mass, Electrospray Ionization; D013656:Taurocholic Acid / Q000097:blood*
D002247:Carbon Isotopes; D007477:Ions; D004364:Pharmaceutical Preparations; D013656:Taurocholic Acid