Drug-excipient compatibility testing—Identification and characterization of degradation products of phenylephrine in several pharmaceutical formulations against the common cold

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 55; no. 5; pp. 949 - 956
• Main Authors: Douša, Michal, Gibala, Petr, Havlíček, Jaroslav, Plaček, Lukáš, Tkadlecová, Marcela, Břicháč, Jiří
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.07.2011; Elsevier
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Chemistry Techniques, Analytical; Chemistry, Pharmaceutical - methods; Chromatography, High Pressure Liquid - methods; Chromatography, Liquid - methods; common cold; Drug Contamination; drug formulations; Drug Stability; drugs; Excipients - chemistry; Excipients compatibility; Fundamental and applied biological sciences. Psychology; General pharmacology; high performance liquid chromatography; Impurities; ion pair chromatography; Magnetic Resonance Spectroscopy - methods; Mass Spectrometry - methods; Medical sciences; Models, Chemical; nuclear magnetic resonance spectroscopy; Pharmaceutical Preparations - analysis; Pharmacology. Drug treatments; Phenylephrine; Phenylephrine - analysis; Phenylephrine - chemistry; Sucrose - analysis; Excipients compatibility; Impurities; Phenylephrine; Drug; Agonist; Nose disease; Impurity; Antihypotensive agent; Vehicle(excipient); α1-Adrenergic receptor; Common cold; Infection; Characterization; Viral disease; Dosage form; ENT disease; Vasoconstrictor agent; α-Adrenergic receptor agonist; Qualitative analysis; Compatibility; Degradation product
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2011.03.027

Different pharmaceutical preparations against the common cold containing phenylephrine (PHE) and saccharose were studied. New impurities were discovered in these preparations after exposure using isocratic ion-pair chromatography separation on a C18 column. LC–MS and NMR techniques were employed to identify and to fully characterize these new compounds. The products were identified as 1-[5-(hydroxymethyl)-2-furyl]-2-methyl-1,2,3,4-tetrahydroisochinolin-4,8-diol and 1-[5-(hydroxymethyl)-2-furyl]-2-methyl-1,2,3,4-tetrahydroisochinolin-4,6-diol. Identification of these degradation products allowed to understand and to confirm their formation mechanism. The developed HPLC method separates of all known impurities and impurities originated from PHE as well.