Darvocet

An example of the use of native silica is in the analysis of Darvocet® and its generic equivalent formulation. The separation obtained is shown in figure 44.

Courtesy of Supelco Inc.

Figure 43 Chromatogram of the Tricyclic Antidepressant Drugs from Blood Serum

Darvocet® is an acetaminophen product of which acetaminophen itself is the active ingredient together with other weakly polar substances present. Consequently, the mixture lends itself to separation on silica gel. The analysis was completed in less than 4 minutes using a short column 3.3 cm long and 4.6 mm in diameter.

The chromatographic conditions were as follows.

Column	LC-PCN
Column Length	25 cm
Column Diameter	4.6 mm
Column Packing	C18 Reverse Phase, (cyanopropile chain)Column Temperature 30oC
Mobile Phase	25%0.01M potassium phosphate (adjusted to pH 7 with 85% phosphoric acid)60% acetonitrile and 15% methanol
Flow-Rate	2 ml/min.
Detector	UV adsorption at 215 nm
Sample Volume	100ml

The silica packing had a particle size of 3 m providing a maximum efficiency of about 5,500 theoretical plates. The column appears to be significantly overloaded in order to identify the impurities, Nevertheless, the impurities were well separated from the main component and the presence of a substance was demonstrated in the generic formulation that was not present in the Darvocet®. The mobile phase consisted of a mixture of 98.5% dichloromethane with 1.5% v/v of methanol containing 3.3% ammonium hydroxide. The ammoniacal methanol deactivated the silica gel but the interaction of the solutes with the stationary phase would still be polar in nature. In contrast solute interactions with the methylene dichloride would be exclusively dispersive.