Use of Thermal Desorption Mass Spectrometry for the Detection of Free Acid Impurities in Pharmaceutical Products
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- 作者：Eric A. Kemp ; Eric D. Nelson ; Randal A. Seburg
- 刊名：Analytical Chemistry
- 出版年：2006
- 出版时间：September 15, 2006
- 年：2006
- 卷：78
- 期：18
- 页码：6595 - 6600
- 全文大小：169K
- 年卷期：v.78,no.18(September 15, 2006)
- ISSN：1520-6882
文摘
A method utilizing thermal desorption mass spectrometry(TDMS) for the detection and quantitation of free acidforms in pharmaceutical drug products formulated assalts is presented. Selective detection of neutral drugforms is possible because the volatility of a drug presentin its free acid form is typically much higher than that ofits corresponding salt forms, which have negligible volatility even at high temperatures. Tandem mass spectrometric detection allows selective quantitation of thedesired free acid drug forms without significant interferences from formulation excipients. The application ofthe TDMS approach is demonstrated for a sodium salt ofa representative, carboxylated drug molecule. Excellentsensitivity, specificity, and adequate linearity of detectorsignal as a function of micrograms of free acid added weredemonstrated in the presence of the sodium salt of thedrug and formulation excipients. The sensitivity of themethod was demonstrated at free acid levels of 0.6% w/w(6 
g absolute mass). Tablet samples were analyzed bythermal desorption EI-MS/MS with reference to externalstandards using a commercially available quadrupole iontrap mass spectrometer. The relative drug form stabilitiesin three different tablet formulations were differentiatedusing this method; the salt-to-free acid form conversionranged between less than the limit of detection to nearcomplete conversion during the stability study.
g absolute mass). Tablet samples were analyzed bythermal desorption EI-MS/MS with reference to externalstandards using a commercially available quadrupole iontrap mass spectrometer. The relative drug form stabilitiesin three different tablet formulations were differentiatedusing this method; the salt-to-free acid form conversionranged between less than the limit of detection to nearcomplete conversion during the stability study.