USP <467> Headspace Residual Solvent Assay with a HT3 Headspace Instrument

February 11, 2011

The Application Notebook

The Application Notebook, The Application Notebook-02-11-2011, Volume 0, Issue 0

The US Pharmacopeia recently released USP<467> as the current monograph for determining residual solvents in pharmaceutical products by static headspace.

Roger Bardsley, Teledyne Tekmar

The US Pharmacopeia recently released USP<467> as the current monograph for determining residual solvents in pharmaceutical products by static headspace. Extensive method validation is not required if the USP parameters are followed. Class 1 and Class 2 residual solvents are determined by the headspace method.

The Class 1 compounds were evaluated from 50% to 500% of the USP limits, while the Class 2 compounds were evaluated from 25% to 400% of the USP limits.

Experimental-Instrument Conditions

The HT3™ headspace instrument sample temperature was set to 80 °C for 45 min in the static mode. The valve oven and transfer line temperature were set to 110 °C as allowed by the USP. A Phenomenex ZB-624 column, 30 m × 0.32 mm × 1.8 µm was selected for the G43 column. A Shimadzu GC-21010 GC/FID was programmed using the GC parameters from the USP method.

Standard Sample Preparation

Class 1, Class 2A, and Class 2B standard stock solutions were prepared following the USP <467> procedure. Analyzing the standards in triplicate demonstrates the compounds reproducibility.

Table I: Signal-to-noise ratio (S/N), percent relative standard deviation (%RSD, n=3), and correlation coefficient (r2) data for the Class 1 compounds with the G43 column

A series of standards were prepared from 50% to 500% of the concentration of the Class 1 Standard. Similar standards from 25% to 400% were generated for the Class 2A and 2B standards. Individually analyzing these samples verified the linearity of the method over these ranges.

Table II: Resolution (R), percent relative standard deviation (%RSD, n=3), and correlation coefficient (r2) data for the Class 2A compounds with the G43 column

Results

Results for the G43 and the G16 columns are presented in Table I for the Class 1 compounds, Table II for the Class 2A compounds, and Table III for the Class 2B compounds.

Table III: Percent relative standard deviation (%RSD, n=3) and correlation coefficient (r2) data for the Class 2B compounds with the G43 column

Conclusions

Using a Teledyne Tekmar HT3 headspace instrument with Phenomenex columns and a Shimadzu GC/FID adequately meets the requirements of the recently released USP Chemical Test Monograph <467> for residual solvents.

Teledyne Tekmar

4736 Socialville Foster Road, Mason, OH 45040

tel. (800) 874-2004, fax (531) 229-7050

Website: www.teledynetekmar.com