PMID- 23394260
OWN - NLM
STAT- MEDLINE
DCOM- 20140422
LR  - 20130319
IS  - 1520-6882 (Electronic)
IS  - 0003-2700 (Linking)
VI  - 85
IP  - 6
DP  - 2013 Mar 19
TI  - Rapid and comprehensive impurity profiling of synthetic thyroxine by 
      ultrahigh-performance liquid chromatography-high-resolution mass spectrometry.
PG  - 3309-17
LID - 10.1021/ac303722j [doi]
AB  - Rapid and efficient quality control according to the public authority regulations 
      is mandatory to guarantee safety of the pharmaceuticals and to save resources in 
      the pharmaceutical industry. In the case of so-called "grandfather products" like 
      the synthetic thyroid hormone thyroxine, strict regulations enforce a detailed 
      chemical analysis in order to characterize potentially toxic or pharmacologically 
      relevant impurities. We report a straightforward workflow for the comprehensive 
      impurity profiling of synthetic thyroid hormones and impurities employing 
      ultrahigh-performance liquid chromatography (UHPLC) hyphenated to high-resolution 
      mass spectrometry (HRMS). Five different batches of synthetic thyroxin were 
      analyzed resulting in the detection of 71 impurities within 3 min total analysis 
      time. Structural elucidation of the compounds was accomplished via a combination 
      of accurate mass measurements, computer based calculations of molecular formulas, 
      multistage high-resolution mass spectrometry (HRMS(n)), and nuclear magnetic 
      resonance spectroscopy, which enabled the identification of 71 impurities, of 
      which 47 have been unknown so far. Thirty of the latter were structurally 
      elucidated, including products of deiodination, aliphatic chain oxidation, as 
      well as dimeric compounds as new class of thyroid hormone derivatives. Limits of 
      detection for the thyroid compounds were in the 6 ng/mL range for negative 
      electrospray ionization mass spectrometric detection in full scan mode. Within 
      day and day-to-day repeatabilities of retention times and peak areas were below 
      0.5% and 3.5% R.SD. The performance characteristics of the method in terms of 
      robustness and information content clearly show that UHPLC-HRMS is adequate for 
      the rapid and reliable detection, identification, and semiquantitative 
      determination of trace levels of impurities in synthetic pharmaceuticals.
FAU - Neu, Volker
AU  - Neu V
AD  - Department of Molecular Biology, Division of Chemistry and Bioanalytics, 
      University of Salzburg, Salzburg, Austria.
FAU - Bielow, Chris
AU  - Bielow C
FAU - Gostomski, Iris
AU  - Gostomski I
FAU - Wintringer, Reiner
AU  - Wintringer R
FAU - Braun, Ralf
AU  - Braun R
FAU - Reinert, Knut
AU  - Reinert K
FAU - Schneider, Peter
AU  - Schneider P
FAU - Stuppner, Hermann
AU  - Stuppner H
FAU - Huber, Christian G
AU  - Huber CG
LA  - eng
PT  - Journal Article
DEP - 20130228
PL  - United States
TA  - Anal Chem
JT  - Analytical chemistry
JID - 0370536
RN  - Q51BO43MG4 (Thyroxine)
SB  - IM
MH  - Chromatography, High Pressure Liquid/methods
MH  - *Drug Contamination
MH  - Mass Spectrometry/*methods
MH  - Thyroxine/*analysis
MH  - Time Factors
EDAT- 2013/02/12 06:00
MHDA- 2014/04/23 06:00
CRDT- 2013/02/12 06:00
PHST- 2013/02/12 06:00 [entrez]
PHST- 2013/02/12 06:00 [pubmed]
PHST- 2014/04/23 06:00 [medline]
AID - 10.1021/ac303722j [doi]
PST - ppublish
SO  - Anal Chem. 2013 Mar 19;85(6):3309-17. doi: 10.1021/ac303722j. Epub 2013 Feb 28.