Peak fronting in reversed-phase high-performance liquid chromatography: a study of the chromatographic behavior of oxycodone hydrochloride.
Severe peak asymmetry--fronting--was observed for oxycodone during elution at 30 degrees C from a C18 HPLC column using a mobile phase consisting of 14.9% MeOH, 84.5% 0.05 M KH2PO4 (pH 3.0), 0.5% MTBE, and 0.1% TEA. Investigation using deuterium-labeled oxycodone and analysis by LC/MS showed that gem diol and hemiketal adducts of oxycodone formed as a result of the equilibrium addition of water and methanol to the C-6 ketone on oxycodone. As a result of slow equilibrium kinetics at room temperature in aqueous solution, the gem-diol and methyl hemiketal eluted as an unresolved broad band in front of the oxycodone peak. Decreasing the column temperature to 0 degrees C decreased the rates of interconversion and allowed the resolution and separation of these species from each other and from oxycodone. Increasing the column temperature to 60 degrees C increased the rates of interconversion with the result that the three species eluted as a single, homogenous peak with greatly improved peak symmetry.
Broglé
K
K
Purdue Research Center, Purdue Pharma L.P., Ardsley, NY 10502, USA.
Ornaf
R M
RM
Wu
D
D
Palermo
P J
PJ
D000701:Analgesics, Opioid / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003903:Deuterium; D007553:Isotope Labeling; D007700:Kinetics; D008968:Molecular Conformation; D009904:Optical Rotation; D010098:Oxycodone / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013696:Temperature
D000701:Analgesics, Opioid; D003903:Deuterium; D010098:Oxycodone