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Mesityl oxide (4-methyl- 3-penten-2-one) is an intermediate product in the synthesis of some drugs. It is produced by aldol condensation of acetone followed by dehydration. This is considered to have a potential genotoxic impurity in drugs due to its alpha-unsaturated ketone structure. Genotoxic compounds damage DNA and cause mutations or cancer. Therefore, concentration of genotoxic impurities in pharmaceutical compounds must be restricted up to a certain limit. A gas chromatographic with electron ionization mass spectroscopy method can determine concentration of mesityl oxide in enalapril maleate.

(a) Citation:

Authors: Ming Peng, Hongliang Wen, Jian Le, and Yongjian Yang

Title: Trace-level analysis of mesityl oxide in enalapril maleate by gas chromatography with electron ionization mass spectrometry (GC-EI-MS)

Journal name: Analytical Methods

Year: 2012

Volume: 4(12)

Pages: 4063-4065

(b) The instrumental method used here was electron ionization/selective ion monitoring (EI/SIM) method.

The measurements for this procedure were carried out using a 7890A GC system coupled to a 7000A triple quadrupole mass spectrometer (Agilent, Santa Clara, CA, USA).

Electron ionization (EI), used in gas chromatography鈥搈ass spectrometry (GC鈥揗S) helps to ionize and fragment analyte molecules before mass spectrometric analysis and detection. Combining the two processes of gas chromatography and mass spectrometry reduces the possibility of error.

(c) An HP 1 ms fused silica capillary column was used with 30 m脳 0.25 mm I.D., 0.25 碌m film thickness (J&W Scientific, Folsom, CA, USA)

(d) The international standard curve method was used as the quantification method of mesityl oxide in sample solution and in recovery solution.

(e) For validation test the retention times of mesityl oxide peak and IS peak in reference standard solution were compared with the ones in sample solution and recovery solution. The relative deviation of the peak retention times should be within 卤 2%.

This method has an excellent measurement precision (relative standard deviation = 0.9%) and accuracy (relative difference鈮�2.29%).

The limit of detection in this method is 0.05 ng.

The limit of quantitation in this method is 0.18 ng

The limit of detection (LOD) and limit of quantification (LOQ) were determined by spiking the decreasing concentration of mesityl oxide in sample solution.

The accuracy and precision determination of mesityl oxide from the literature is shown below:

The quantification of mesityl oxide was linear in the concentration range from 0.18 to 7.17 碌g/mL, corresponding to 1.8 ~ 72 碌g/g in enalapril maleate.The linear regression equation obtained was Y锛�(0.3170卤0.016) X+(-0.1250卤0.0417), r²=0.996(n=8)

(f) A standard solution can be used for 24 hr.