Related Experiment Video
Updated: Jul 28, 2026
13:35
A Convenient Method for Extraction and Analysis with High-Pressure Liquid Chromatography of Catecholamine Neurotransmitters and Their Metabolites
Published on: March 1, 2018
NMR regulatory analysis: enantiomeric purity determination for (R)-(-)-desoxyephedrine and antipode methamphetamine
1US Department of Health and Human Services, Food and Drug Administration, Northeast Regional Laboratory, Jamaica, New York, 11435-1034, USA.
Die Pharmazie
|April 8, 2006
Summary
NMR spectroscopy enables direct determination of enantiomeric purity for methamphetamine and desoxyephedrine using a chiral solvating agent. This method accurately quantifies enantiomers, crucial for regulatory and pharmaceutical applications.
Area of Science:
- Analytical Chemistry
- Spectroscopy
- Organic Chemistry
Background:
- Enantiomeric purity is critical for pharmaceuticals and controlled substances.
- Accurate quantification of enantiomers is essential for regulatory compliance.
- Existing methods for enantiomeric purity determination can be complex and time-consuming.
Purpose of the Study:
- To develop a direct method for determining the enantiomeric purity of (S)-(+)-methamphetamine and (R)-(-)-desoxyephedrine.
- To utilize 400 MHz 1H NMR spectroscopy with a chiral solvating agent for enantiomeric differentiation.
- To establish a reliable and accurate quantification method for enantiomeric mixtures.
Main Methods:
- Utilized 400 MHz 1H NMR spectroscopy.
- Employed a diamagnetic chiral solvating agent to differentiate enantiomers.
- Studied the nonequivalence behavior of fast diastereomeric solvates.
- Optimized experimental conditions for signal resolution and quantification.
Main Results:
- Achieved efficient enantiomeric differentiation of (S)-(+)-methamphetamine and (R)-(-)-desoxyephedrine.
- Resolved enantiomeric signals suitable for quantification were obtained.
- Demonstrated excellent agreement between determined and known enantiomer values in synthetic mixtures.
- Reported high recovery rates for the (R)-(-)-enantiomer (99.9 +/- 0.4%).
Conclusions:
- The developed 1H NMR method provides direct and accurate enantiomeric purity determination.
- The method is suitable for regulatory analysis of controlled substances and pharmaceuticals.
- Optimization allows for sensitive detection and quantification of enantiomers.
Related Concept Videos
02:24Properties of Enantiomers and Optical Activity
It is essential to understand the difference between chiral and achiral interactions and the implications thereof in optical activity and their applications. Just as our feet, which are chiral, interact uniquely with chiral objects, such as a pair of shoes, but identically with achiral socks, enantiomers of a molecule exhibit different properties only when they interact with other chiral media. An example of a significant implication from this facet is the phenomenon known as optical activity,...
02:30Racemic Mixtures and the Resolution of Enantiomers
A racemic mixture, or racemate, is an equimolar mixture of enantiomers of a molecule that can be separated using their unique interaction with chiral molecules or media. Racemic mixtures are denoted by the (±)- prefix. This ‘optical rotation descriptor’ applies to the whole solution of a racemic mixture rather than a specific stereoisomer. Enantiomers typically have the same physical and chemical properties. Hence, they are not easily separable. However, enantiomers can exhibit different...
02:30Chirality at Nitrogen, Phosphorus, and Sulfur
Chirality is most prevalent in carbon-based tetrahedral compounds, but this important facet of molecular symmetry extends to sp3-hybridized nitrogen, phosphorus and sulfur centers, including trivalent molecules with lone pairs. Here, the lone pair behaves as a functional group in addition to the other three substituents to form an analogous tetrahedral center that can be chiral.
A consequence of chirality is the need for enantiomeric resolution. While this is theoretically possible for all...
A consequence of chirality is the need for enantiomeric resolution. While this is theoretically possible for all...
00:58¹H NMR Chemical Shift Equivalence: Enantiotopic and Diastereotopic Protons
Replacing each alpha-hydrogen in chloroethane by bromine (or a different functional group) yields a pair of enantiomers. Such protons are called prochiral or enantiotopic and are related by a mirror plane. Enantiotopic protons are chemically equivalent in an achiral environment. Because most proton NMR spectra are recorded using achiral solvents, enantiotopic hydrogens yield a single signal.
In chiral compounds such as 2-butanol, replacing the methylene hydrogens at C3 produces a pair of...
In chiral compounds such as 2-butanol, replacing the methylene hydrogens at C3 produces a pair of...
01:28Adrenergic Agonists: Mixed-Action Agents
Mixed-action adrenergic agonists, like ephedrine and pseudoephedrine, directly and indirectly affect adrenergic receptors. These agents stimulate adrenoceptors and indirectly release stored neurotransmitters, amplifying the adrenergic response.
Ephedrine and pseudoephedrine lack a catecholamine group, making them less susceptible to degradation by metabolic enzymes. They have increased oral bioavailability and lipophilicity, resulting in a longer duration of action. Their response is reduced by...
Ephedrine and pseudoephedrine lack a catecholamine group, making them less susceptible to degradation by metabolic enzymes. They have increased oral bioavailability and lipophilicity, resulting in a longer duration of action. Their response is reduced by...
01:16Adrenergic Agonists: Chemistry and Structure-Activity Relationship
Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...