Determination of the Enantiomeric Purity of Dextromethorphan Hydrobromide

Dextromethorphan, the dextrorotatory enantiomer of methorphan, serves as an antitussive drug. According to the US pharmacopoeia, the optical rotation of dextromethorphan hydrobromide has to be measured at a wavelength of 325 nm whereas the EU pharmacopoeia

Methorphan - Two different pharmacological effects

Methorphan is a chiral drug that differs in its effects and pharmacology with respect to its two enantiomers. The dextrorotatory dextromethorphan is used as an antitussive drug in cough medicines, whereas the levorotatory enantiomer levomethorphan is a strong opioid analgesic that is listed as a schedule II drug in the United States. As dextromethorphan is approved for use in over-the-counter drugs, accurate control of enantiomeric purity is essential.

The US pharmacopoeia demands the determination of optical rotation of dextromethorphan at a concentration of 18 mg/mL in water. At the standard wavelength of 589.3 nm the optical rotation is 0.504° under these conditions. A lower wavelength results in an increased optical rotation (+ 4.68° at 325 nm) that also correlates with a higher sensitivity of the measurement.

In contrast, the EU pharmacopoeia demands the determination of the specific rotation of 20 mg/mL dextromethorphan hydrocloride in 0.1 M hydrochloric acid at 589 nm and 20 °C.

Determining the enantiomeric purity of dextromethorphan

Anton Paar’s MCP 500 polarimeter with multiwavelength function is ideal for determining the optical rotation of dextromethorphan according to the US pharmacopoeia. If the measurement is carried out according to the EU, MCP 100/200/300 are also suitable.

The MCP 500 with multiwavelength function allows the most precise analysis of dextromethorphan in the milligram range due to the high resolution range of up to 0.0001° optical rotation. Moreover, an integrated Peltier element allows temperature control with an accuracy of up to ±0.03 °C. On top of that, a built-in camera system helps to verify the correct filling of the sample cell in order to avoid air bubbles or smears. 

The analysis of dextromethorphan hydrobromide with polarimetry is further specified in the corresponding Application Report.

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Good to know

According to international pharmacopoeias, enantiomeric purity can be determined via optical rotation measurement.