title: Detection of low-abundance impurities in synthetic thyroid hormones by stationary phase optimized liquid chromatography-mass spectrometry.
abstract: The transfer of a gradient method to an isocratic or multistep gradient method employing stationary phase optimized liquid chromatography facilitated a reduction in analysis time by 50% and significantly improved the mass spectrometric detectability of impurities in synthetic thyroid hormones. Four column segments packed with different stationary phases were combined into a single chromatographic column, which allowed the separation and photometric as well as mass spectrometric detection of thyroid compounds in less than 30 min under isocratic- or step gradient elution conditions with 0.10% acetic acid/acetonitrile. Signal instability and baseline drift during detection by negative electrospray ionization time-of-flight mass spectrometry were minimized by optimizing the spray parameters for each individual elution step. This resulted in improved detectabilities and higher mass spectral quality, especially for low-abundance components in the sample mixture. The method was applied to the separation and detection of the low-abundance impurities formed upon the thermal stressing of a sample of synthetic levothyroxine.
authors.affiliation: Instrumental Analysis and Bioanalysis, Department of Chemistry, Saarland University, P.O. Box 151150, 66041, Saarbrücken, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Gostomski
authors.forename: Ralf
authors.initials: R
authors.lastname: Braun
authors.forename: Christian G
authors.initials: CG
authors.lastname: Huber
mesh_terms: D002138:Calibration; D002626:Chemistry, Pharmaceutical; D002853:Chromatography, Liquid / Q000379:methods; D004340:Drug Contamination / Q000517:prevention & control; D013058:Mass Spectrometry / Q000379:methods; D011786:Quality Control; D012680:Sensitivity and Specificity; D013963:Thyroid Hormones / Q000737:chemistry*
chemical_list: D013963:Thyroid Hormones