title: Esterification of pseudoephedrine hydrochloride by citric acid in a solid dose pharmaceutical preparation.
abstract: Esterification of pseudoephedrine hydrochloride (PSE) by citric acid was observed in a solid dose pharmaceutical preparation at room temperature and accelerated stability condition (40°C/75% relative humidity). The esterification of PSE with citric acid was confirmed by a solid-state binary reaction in the presence of minor level of water at elevated temperature to generate three isomeric esters. The structures of the pseudoephedrine citric acid esters were elucidated using high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy (NMR). Occurrence of esterification in solid state, instead of amidation which is generally more favorable than esterification, is likely due to remaining HCl salt form of solid pseudoephedrine hydrochloride to protect its amino group from amidation with citric acid. In contrast, the esterification was not observed from solution reaction between PSE and citric acid.
authors.affiliation: Analytical Research and Development, McNeil Consumer Healthcare, 890 Woodlawn Road West, Guelph, Ontario, N1K 1A5, Canada. Electronic address: agoel2@its.jnj.com.
authors.forename: Alok
authors.initials: A
authors.lastname: Goel
authors.affiliation: Analytical Development, Johnson & Johnson Family of Consumer Companies, Skillman, NJ 08558, USA.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, L8S 4M1, Canada.
authors.forename: Dan
authors.initials: D
authors.lastname: Sørensen
authors.affiliation: Analytical Development, Johnson & Johnson Family of Consumer Companies, Skillman, NJ 08558, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Analytical Development, Johnson & Johnson Family of Consumer Companies, Skillman, NJ 08558, USA. Electronic address: fzhang1@its.jnj.com.
authors.forename: Fa
authors.initials: F
authors.lastname: Zhang
mesh_terms: D019343:Citric Acid / Q000737:chemistry*; D004951:Esterification; D004952:Esters / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D019999:Pharmaceutical Solutions / Q000737:chemistry*; D054199:Pseudoephedrine / Q000737:chemistry*
chemical_list: D004952:Esters; D019999:Pharmaceutical Solutions; D019343:Citric Acid; D054199:Pseudoephedrine
keywords: Citric acid; Esterification; HPLC–MS; NMR; Pseudoephedrine hydrochloride