Pros and cons on the use of dimethyl carbonate as green organic modifier in liquid chromatography

Reversed-phase liquid chromatography (RPLC) is the most widely employed analytical method in (bio)pharmaceutical industry, not only for analytical purposes but also for preparative scopes, to isolate the target (bio)pharmaceutical with elevated purity. The most widely employed organic modifier in RPLC is acetonitrile due to its exceptional characteristics, such as high elution strength, UV transparency, high miscibility with water and low viscosity. However, it is slightly toxic by acute exposure through oral intake, skin contact, and inhalation and it can be converted by the body into cyanide. [1] For this reason, in the last year the greening of analytical methods has gained increasing interest in the pharmaceutical field, in order to reduce the environmental impact commonly associated with manufacturing process and to ensure health safety of operators. Indeed, especially in preparative conditions, the large amount of solvents commonly employed leads to the generation of high quantities of waste to be disposed. [2] Beside alcohols, whose physico-chemical properties are well-known, also less common solvents have recently attracted the attention for this purpose. One of this is dimethyl carbonate (DMC), which is classified among the “recommended” biodegradable and not toxic solvents. [3] DMC has been introduced as organic solvent for LC only recently, and it was demonstrated that it could be applied in LC hyphenated to inductively coupled plasma mass spectrometry platforms. [4] In this work, the possibility of using DMC as organic modifier in LC with UV-Vis detection will be discussed through a series of case studies including fundamental studies on retention in linear conditions up to applications in preparative conditions for the purification of pharmaceutically relevant peptides. Literature: [1] www.epa.gov [2] M. Yabré et al., Molecules. 2018, 23, 1065. [3] D. Prat et al, Green Chem. 2016,18, 288 [4] B. Lajin et al., J. Anal. At. Spectrom. 2021,36, 1272