S-adenosyl-L-methionine (SAM), analysis and formulation specifics

S-adenosyl-L-methionine (SAM), synthesized from methionine and adenosine triphosphate (ATP), is an endogenous metabolite present in all living organisms. SAM exists in two diastereoisomeric forms: the biologically active isomer (S,S)-S-adenosyl-methionine and (R,S)-S-adenosyl-methionine. In humans, SAM levels decrease with age, and its deficiency leads to metabolic changes and transmethylation disorders associated with various diseases. Due to its numerous physiological functions, SAM is used for treatment of liver diseases, depression, fibromyalgia, osteoarthritis, and Alzheimer’s disease.

SAM FORMULATIONS

Oral formulations of SAM have been marketed worldwide as dietary supplements and as pharmaceutical products in daily doses ranging from 200 mg to 1600 mg. In formulations, S,S- SAM tends to isomerize until an equilibrium ratio of 1:1 is reached between the two diastereoisomers. One of the main problems with formulations containing SAM is its high chemical instability, as it breaks down rapidly even at room temperature, in the presence of moisture, and at certain pH values. The stability of SAM is improved in the form of the salt of a strong acid. On the market, SAM is usually found in the form of salts of sulfuric acid, 1,4-butanedisulfonic acid, and p-toluenesulfonic acid (tosylated salts).

Despite its high solubility, SAM has poor systemic bioavailability. To counteract oral administration and rapid metabolism, high doses are usually used. Although no toxic side effects have been noted with the use of SAM in high doses, the low content of the active ingredient in the oral formulations may severely compromise the efficacy of the product in the intended treatment. The marketing of SAM implies that higher doses are needed to stimulate methylation and improve health. Analysis of the marketed food supplements has shown that in many commercially available food products claiming to contain SAM, the content was far below the value indicated on the label, which may be due to either the use of an unstable form or improper manufacturing.

QUALITY CONTROL

The pharmacological potential of SAM urges finding formulations that ensure the stability of the molecule and a better pharmacokinetic profile. Therefore, to ensure the quality and efficacy of the product, it is necessary to perform proper analytical control of the active ingredients in the formulation: from the raw material to the entire life cycle of the product. Improving the formulation in the early stages of product development is essential to increase the value of the product and reduce manufacturing costs while ensuring the consistency and safety of the dietary supplements.

In our laboratory, we perform analysis of SAM according to pharmacopeia monograph and industry guidelines using a validated high-performance liquid chromatography method.

If you need analytical support during product development, stability studies or in-process quality control, Contact us.