Can prescription methamphetamine contain both d- and l-isomers?

From the Guidelines

Prescription methamphetamine, typically formulated as the d-isomer, can contain both d- and l-isomers, although the d-isomer is more commonly used due to its stronger central nervous system effects. The provided evidence does not directly address the composition of prescription methamphetamine [ 1 ]. However, it is known that the d-isomer (dextromethamphetamine) has stronger central nervous system effects, making it more effective for treating conditions like ADHD and narcolepsy. In contrast, the l-isomer (levomethamphetamine) has weaker central nervous system effects but stronger peripheral effects, such as decongestant properties [ 1 ].

Some key points to consider:

• The presence of both isomers in a legal preparation depends on the specific medication's intended use and the manufacturing process.
• The different isomers have distinct pharmacological profiles because they interact differently with receptors in the body due to their three-dimensional structures, despite having the same chemical formula.
• Prescription methamphetamine (brand name Desoxyn) is typically formulated as the d-isomer, but some pharmaceutical preparations may contain a mixture of both isomers [ 1 ].
• The choice of medication and dosing regimen can affect treatment outcomes, and individual factors such as severity of symptoms, presence of comorbidities, and patient preferences should be considered when selecting a medication [ 1 ].

In clinical practice, the specific composition of prescription methamphetamine may vary, and healthcare providers should be aware of the potential differences in pharmacological effects between the d- and l-isomers [ 1 ].

From the FDA Drug Label

Methamphetamine hydrochloride, USP, chemically known as (αS)-α-Methylbenzeneethan-(N-methyl)-amine Hydrochloride, is a member of the amphetamine group of sympathomimetic amines. The prescription methamphetamine contains the (αS) isomer, which refers to the d-isomer. There is no mention of the l-isomer in the drug label.

• The drug label only mentions the d-isomer.
• No information is provided about the presence of both d- and l-isomers together. 2

From the Research

Prescription Methamphetamine Composition

• Prescription methamphetamine can contain both d- and l-isomers, as the enantiomeric composition of methamphetamine is important in determining its source and use 3.
• The presence of both d- and l-isomers in a sample can indicate the use of a controlled substance, while the presence of only the l-isomer may suggest the use of a non-controlled substance, such as the Vick's Inhaler 3.
• The enantiomeric distribution of amphetamine can provide unambiguous interpretation of methamphetamine use, with the detection of the d-enantiomer or a mixture of d- and l-enantiomers indicating the use of a controlled substance 3.

Analytical Methods for Enantiomer Detection

• Various analytical methods, such as liquid chromatography-mass spectrometry (LC-MS-MS) and gas chromatography-mass spectrometry (GC-MS), can be used to detect and quantify the d- and l-isomers of methamphetamine 4, 5.
• Chiral stationary phase (CSP) LC-MS-MS has been shown to be a reliable and accurate method for the enantiomeric separation of methamphetamine, with lower error rates compared to GC-MS 5.
• High-performance liquid chromatography (HPLC) with chiral columns can also be used to separate and quantify the d- and l-isomers of methamphetamine and amphetamine 6, 7.

Clinical and Forensic Applications

• The detection and quantification of d- and l-isomers of methamphetamine can have important implications in clinical and forensic settings, such as in the diagnosis and treatment of methamphetamine use disorders, and in the investigation of methamphetamine-related crimes 4, 5, 6, 7, 3.
• The use of enantiomeric characterization of methamphetamine can help to distinguish between legitimate and illicit use of the drug, and can provide valuable information for medical and legal professionals 3.