Use of a green (bio) solvent – limonene – as extractant and immiscible diluent for large volume injection in the RPLC‐tandem MS assay of statins and related metabolites in human plasma

Abstract

Limonene, considered a green solvent, was successfully used to extract simvastatin, lovastatin, and their hydroxy-acid metabolites from human plasma samples. The extraction process was followed by the direct injection of a large volume aliquot (100 μL) from the limonene layer into a Zorbax SB-C(18) Rapid Resolution chromatographic column (50 mm length × 4.6 mm i.d. × 1.8 µm d.p.), operated under gradient elution reversed-phase separation mechanism. Tandem mass spectrometry operated under the multiple reaction monitoring mode was used for detection, providing low quantitation limits in the 0.25-0.5 ng/mL concentration interval. This method was validated and used for quantitation of simvastatin and its hydroxy acid metabolite in incurred plasma samples obtained from two volunteers participating in a bioequivalence study, using lovastatin and its hydroxy analog as internal standards. The results were statistically compared with those produced by means of an alternative RPLC-tandem MS using protein precipitation with acetonitrile. The quality attributes of the two methods are comparatively discussed. The agreement between the quality characteristics of the two methods and the experimental results obtained on real samples may be considered as a consistent basis for the simultaneous use of limonene as extraction medium and injection diluent for hydrophobic compounds in bioanalytical approaches.

Physical characterization of eco‐friendly O/W emulsions developed through a strategy based on product engineering principles

“…D‐limonene, a naturally occurring hydrocarbon, is a cyclic monoterpene, which is commonly found in the rinds of citrus fruits such as grapefruit, lemon, lime, and in particular, oranges. D‐limonene exhibits good biodegradability, hence it may be proposed as an interesting alternative to organic solvents . These solvents can meet the ever‐increasing safety and environmental demands of the 21st century.…”

Hydrogenation of unactivated enamines to tertiary amines: rhodium complexes of fluorinated phosphines give marked improvements in catalytic activity

“…This solvent is now being used as a green alternative to hexane in the cleaning industry and extraction [28–30], but barely has been exploited in synthetic chemistry so far [29]. While being an environmentally benign, fairly cheap, waste-derived chemical, it might seem counter-intuitive to use it in hydrogenation since it contains 2 double bonds itself.…”

Sample preparation for large‐scale bioanalytical studies based on liquid chromatographic techniques

“…This approach was checked in several theoretical studies (David, Galaon, & Aboul‐Enein, ; Udrescu, Medvedovici, & David, ), and successfully applied for bioequivalence studies for some drugs (Medvedovici, Udrescu, Albu, Tache, & David, ; Udrescu et al, ). The procedure becomes safer for the technical personal involved in sample preparation when the organic solvent is environmentally friendly, although all organic solvents have adverse effects on the environment (Filippou, Bitas, & Samanidou, ), or more pleasant (limonene) when manipulated for SP (Medvedovici, Udrescu, & David, ).…”