Acetaminophen is an over-the-counter pain and fever reducer, and a major component of cold and flue remedies. Phenylephrine is a decongestant. Guaifenesin is a mucolytic agent used to relieve respiratory difficulties. These three compounds of cough medication were separated by mixed-mode chromatography on a Primesep C HPLC column. Retention and order of elution for phenylephrine can be changed by buffer concentration and buffer pH. Method can be used for analysis of cough and cold composition during the production and in QC/QA environment. Method is compatible with LC/MS and can be used to analyze these components in biological fluids. This generic HPLC method is robust and reproducible.

Method for separation of components of cough medication shows how retention for acetaminophen, phenylephrine and guaifenesin is controlled. Order of elution for compounds can be changed based on composition of the mobile phase. The method is compatible with UV, ELSD and LC/MS and can be used for quantitation of drugs in formulation. Primesep C mixed-mode HPLC column is ideal candidate for analysis of cough compositions. Basic compounds are well retained in mixed-mode chromatography without use of ion-pairing reagents. Several companies validated this approach. The method is reproducible and robust and can be used in both production environments and R&D. This HPLC method can be adopted as general approach for analysis of basic compounds in various mixtures.

NyQuil is a cough medication produced by Procter&Gamble. It consists of acetaminophen, pseudoephedrine, doxylamine and dextromethorphan. Most of the analytical HPLC methods include either use of ion-pairing reagent or a gradient elution. Mixed-mode chromatography allows to replace long gradient method with short isocratic method. All four compounds are well separated within 3-5 minutes. Methods can be optimized for analysis of other cough composition containing general cough suppressants and pain killers. Method is robust and being validated at several drug companies.

Obelisc R column can be successfully used for analysis of hydrophobic and hydrophilic basic and acidic drugs and corresponding counter-ions. This approach can be used for analysis of various cold and cough composition, pain killers, and other prescription and over-the-counter medications. Within pH 3-5, both cation- and anion mechanism are present on the column, along with hydrophobic interaction. Selectivity of this mixed-mode separation is controlled by the amount of acetonitrile, buffer concentration and buffer pH. Method is robust and reproducible, and can be used as a common HPLC method for analysis of drug molecules and compositions.