Determination of the enantiomeric purity of epinephrine by HPLC with circular dichroism detection

Abstract

Several hundred drug substances approved by the U.S. Food and Drug Administration are chiral molecules. For the enantiomeric purity assessment, current practice is to develop separation techniques using chiral columns or mobile phase modifiers to separate enantiomers before detection. An alternative approach is to use currently accepted HPLC assay methods and use chiral-specific detectors to confirm whether the correct enantiomer is present. In this paper, adding a circular dichroism (CD) detector to an achiral HPLC method from the US Pharmacopeia (USP) is shown to be amenable for the determination of the enantiomeric purity of epinephrine, a substance used to treat anaphylaxis. This HPLC-UV-CD approach was able to detect the inactive D-(+) enantiomer at 1% of the total epinephrine composition. The linearity, accuracy, and precision of HPLC-UV-CD were evaluated and compared to analyses using a chiral HPLC method. Additionally, an epinephrine drug product was analyzed for assay (concentration) and enantiomeric purity. The results from achiral and chiral methods were identical within the experimental error. Overall, achiral chromatography performed using a USP method with CD detection may serve as a general means of determining chiral drug enantiomer purity and avoids the need for the development of additional chiral-specific methods for each individual drug.

Chiral Purity of Crystals Using Low‐Frequency Raman Spectroscopy

“…Finally, epinephrine was chosen to demonstrate the application of LF‐Raman for chiral purity investigation of drugs, as only the L‐enantiomer is biologically active, emphasizing the importance of chiral separation. Figure a presents the LF‐Raman spectra of L‐epinephrine and DL‐epinephrine.…”

“…An example for different properties of enantiomers is the odor of limonene; while the D‐enantiomer has a lemon‐like smell, the L‐enantiomer has an orange‐like smell . A good example for reduction in efficiency is the drug epinephrine, where only the L‐enantiomer is biologically active ,. For these reasons and others, it is extremely important to achieve chiral separation and obtain products with sufficient enantiomeric purity…”

An Evaluation of the Drone Delivery of Adrenaline Auto-Injectors for Anaphylaxis: Pharmacists’ Perceptions, Acceptance, and Concerns

“…As a result, this causes a decrease in Active Pharmaceutical Ingredient (API) potency [28] within formulations and a reduced health outcome; thus, it is vital to maintain the dose uniformity with respect to (−)-adrenaline. Circular dichroism spectroscopy [35] (CD) has been used in this study to simultaneously analyse the chiral composition, concentration, and enantiomeric stability of adrenaline formulations. The presence of (+)-adrenaline and changes in adrenaline concentration outside of the British Pharmacopeia [36] (BP) label claim (%) have been selected as the indicators of instability.…”

Fluorescence Sensing Platforms for Epinephrine Detection Based on Low Temperature Cofired Ceramics

“…However, because of the similarity of EP structure to the wide range of metabolites, e.g., amino acids, and also because of potential interference from drugs or their metabolites, an accurate and sensitive technique for EP detection presents numerous complications. Commonly used analytical procedures for epinephrine determination, such as liquid chromatography [7], spectrophotometric [8], capillary electrophoresis [9], fluorometric [10], high pressure liquid chromatography and circular dichroism [11], may not present satisfactory detection limits, low selectivity and high costs, and are time consuming. Taking that into consideration, biosensors are good alternative for these methods.…”