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.

Mixed-mode chromatography allows to separate various hydrophobic and hydrophilic drugs in one HPLC method. Presence of at least two mechanism of retention allows adjust selectivity of separation by changing three parameters: amount of acetonitrile, buffer concentration and buffer pH. Seven common drugs are separated on an Obelisc R trimodal HPLC column in gradient method. Method provides alternative selectivity to traditional reversed-phase chromatography. Operational range in which basic compounds are retained the most is from pH 3 to 5. At higher pH, longer retention can be achieved. Mixed-mode chromatography provides longer retention and better peak shapes for basic and acidic analytes. Method can be used in analysis of drugs and pharmaceuticals.

Common hydrophobic basic and hydrophilic basic drugs are separated by mixed-mode chromatography with greater selectivity and resolution than traditional reversed-phase column. Drugs are retained by combination of reversed-phase and cation-exchange mechanisms. Retention time is controlled by amount of acetonitrile, buffer concentration and buffer pH. Available detection techniques are based on buffer selection and include UV, Evaporative Light-Scattering Detector (ELSD), Corona (CAD), LC/MS, etc. This HPLC method can be adopted as general approach for analysis of drugs and pharmaceuticals.