Digestion of Difficult APIs in Accordance with USP


Application Notebook

Application NotebookApplication Notebook-09-01-2017
Volume 32
Issue 9

The new USP Chapters <232> and <233> will become official on January 1, 2018 and bring significant changes in sample preparation and analysis of pharmaceutical samples both in excipients and APIs. Certain APIs pose challenges to acid digestion because they are very stable compounds and not easily broken down.

USP methods <232> and <233> call for total digestion of pharmaceutical samples and quantification of individual elements. Many pharmaceutical materials can be easily digested but APIs with multiple aromatic ring structures can be very difficult to completely break down and obtain a clear digestion, as prescribed in the new chapters. Microwave digestion can provide a solution to many of these compounds.

This application note will focus on the use of the CEM MARS 6 microwave digestion system and new high performance iPrep vessels to completely digest very difficult APIs. The ring structures of the APIs are shown to illustrate the high stability of these compounds. The sample sizes listed represent the maximum allowable in order to achieve a complete digest.

Experimental Conditions

Three APIs were prepared using a CEM MARS 6 microwave digestion system equipped with iWave technology and iPrep vessels.

iWave is a novel Light Emitting Technology(tm) that measures the temperature of the actual sample solution inside the vessel and does not require an internal probe.

iPrep is a simple to use three-piece vessel which uses a simple hand torque device to seal. The patented dual-seal design provides for higher temperatures and fine control of the vent and reseal process necessary for these sample types.

Each API sample was weighed and added to an iPrep liner with 9 mL HNO3 and 1 mL HCl. The vessels were capped, assembled, and placed in the MARS 6 for digestion. Digestion parameters are recorded in Table I.


The MARS 6 with iPrep vessels was able to completely digest each of the API materials and provide a clear solution. Of note is that the TrixiPhos digestate is a bright yellow color. This is a result of the Pd catalyst used when synthesizing the compound. Each API sample was run in duplicate in order to confirm the success of the sample preparation. All samples were completely digested as shown in Figure 1.


The MARS 6 system with iPrep vessels is an ideal option for working with these difficult pharmaceutical materials.

CEM Corporation
P.O. Box 200, Matthews, NC 28106
tel. (704) 821-7015, (800) 726-3331
Website: www.cem.com