Use of Mass Spectrometry Methods as a Strategy for Detection and Determination of Residual Solvents in Pharmaceutical Products

详细信息    查看全文

• 作者：José ; Luis Pé ; rez Pavó ; n ; Miguel del Nogal Sá ; nchez ; Carmelo Garc&iacute ; a Pinto ; M. Esther Ferná ; ndez Laespada ; and Bernardo Moreno Cordero
• 刊名：Analytical Chemistry
• 出版年：2006
• 出版时间：July 15, 2006
• 年：2006
• 卷：78
• 期：14
• 页码：4901 - 4908
• 全文大小：277K
• 年卷期：v.78,no.14(July 15, 2006)
• ISSN：1520-6882

文摘

In the present work a strategy for the qualitative andquantitative analysis of residual solvents in pharmaceutical products is reported. First, a low-resolution chromatogram is generated for the identification of the solventspresent in the samples by means of headspace generation-fast gas chromatography-mass spectrometry (HS-fastGC/MS). From the plotting of this information by meansof contour plots with time and mass/charge axes, it isdecided whether quantification of such compounds canbe accomplished without chromatographic separation orwhether it should be done by fast gas chromatography.The nonseparative method is based on direct coupling ofa headspace sampler with a mass spectrometer (HS-MS)and requires a signal recording time of only 3 min, whilewith fast gas chromatography the time required to obtaina chromatogram is 7.16 min. The use of headspacegeneration for introducing the sample and standard addition as a quantification technique provided satisfactoryresults and minimized the matrix effect. An importantadvantage of the methodologies used here is related tothe fact that no prior treatment of the sample is required,thus minimizing the creation of analytical artifacts and theerrors associated with this step of the analytical process.The methods were applied to the determination of residualsolvents in 27 different pharmaceutical products. Detection and quantitation limits were sufficiently low to enablethe estimation of organic volatile impurities according tothe International Conference on Harmonization (ICH) ofTechnical Requirements for the Registration of Pharmaceuticals for Human Use.