Rapid stereoselective separations of amphetamine derivatives with highly sulfated γ-cyclodextrin

Abstract

The highly sulfated gamma-CD (HS-gamma-CD) is a chiral selector widely used in CE for the enantioseparation of pharmaceutical compounds. This paper investigated different approaches to reduce the stereoselective analysis time of amphetamine (AT) derivatives according to the chiral selector concentration in the BGE. With high HS-gamma-CD concentration, tested analytes were separated in 3.5 min as anionic complexes with short-end injection technique in reversed polarity mode. However, this procedure presented some limitations in terms of efficiency and resolution, excessive Joule heating and poor compatibility with MS detection. With low HS-gamma-CD concentration, compounds were separated as cations. Conventional approaches to reduce CE analysis time demonstrated critical resolution between some analytes. Therefore, the use of the partial-filling technique compatible with MS detection was carried out. Under optimized conditions, the analysis time for the chiral separation of seven AT like compounds was reduced to 6 min. Moreover, sensitivity of CE-MS was sufficient for the determination of ATs in plasma following a simple liquid-liquid extraction.

Sensitive chiral analysis by CE: An update

“…Thus, Table 1 shows the use of LLE for the determination of drugs in biological samples as plasma [20][21][22][23], human serum [17,19], human urine [17], and a microsomal fraction of liver homogenates [18]. Preconcentration factors up to 21 were achieved by this extraction procedure.…”

“…Preconcentration factors up to 21 were achieved by this extraction procedure. After this sample treatment step, LODs from 10 26 to 3610 28 M were reported when UV detection was used [17][18][19][20] and LODs ranging form 3610 26 to 4610 29 M were reached with ESI-MS detection [21,22]. As example, Schappler et al [22] assessed two approaches to enhance the sensitivity in CE.…”

“…The different strategies used to avoid the entrance of the chiral selector into the mass analyzer, preventing a deterioration of the sensitivity, were the partial filling of the capillary with the separation media containing the chiral selector in combination with anionic CDs migrating in countercurrent [21,22] or the use of anionic CDs migrating in countercurrent with suppressed EOF [43]. Table 3 reveals that LODs reached in works using EKC-ESI-MS were comprised from 3610 25 to 4610 29 M. Rudaz et al used the countercurrent migration of the negatively charged highly sulfated-g-CD (HS-g-CD) and the partial-filling technique to achieve the enantioseparation of amphetamine derivatives [21,22]. The countercurrent migration technique is based on the control of the apparent mobility of the chiral selector to avoid that it reaches the MS detector, whereas in the partial-filling technique, a zone of the capillary (where the enantiomeric separation takes place) is filled with BGE containing the chiral selector while the zone close to the MS detector only contain buffer without chiral selector.…”

Application of Carbon Nanotubes in Chiral and Achiral Separations of Pharmaceuticals, Biologics and Chemicals

“…Electrokinetic chromatography (EKC) has been widely applied for enantioseparations having the following advantages, high resolution, efficient separation, cost effective and only requires low quantities of samples and [61,84] reagents. Enantiomeric separation occurs in EKC when a chiral selector such as β-CD is added to a pseudostationary phase [85]. Enantiomeric separation has been also studied using chiral surfactants as pseudo-stationary phases in a system called microemulsion EKC (MEEKC) [86,87].…”

18 Coupling CE and microchip-based devices with mass spectrometry

“…As a result, the generated current generally did not exceed the instrument limitation even when high voltage was applied, which led to high efficiencies. 205 …”