SFC for chiral separations in bioanalysis

Harps, Lukas Corbinian; Joseph, Jan Felix; Parr, Maria Kristina

doi:10.1016/j.jpba.2018.08.061

Cited by 51 publications

(31 citation statements)

References 69 publications

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“…Contrary to previous reports of peaks narrowing as temperature rises [22], we observed better peak shapes and chiral resolution as temperature declined with the best performance at sub-ambient temperatures (15 °C). Method development for SFC methods generally entails the screening of temperatures from 25–60 °C [39] and sometimes ambient temperatures [37,40], however, sub-ambient temperature working conditions, here tentatively termed SubFC, proved superior in the case of analytes that otherwise resisted chiral resolution (K). Indeed, while higher temperatures are known to affect the chiral recognition ability of polymeric CSPs through the induction of—often irreversible—conformational changes [41], lower temperatures may increase the rigidity of the polysaccharide back bone resulting in higher accessibility to the chiral ravines, within which enantio-selective hydrogen bonding is responsible for chiral recognition [42].…”

Section: Discussionmentioning

confidence: 99%

Subcritical Fluid Chromatography at Sub-Ambient Temperatures for the Chiral Resolution of Ketamine Metabolites with Rapid-Onset Antidepressant Effects

et al. 2019

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Chiral metabolites of ketamine exerting rapid-onset yet sustained antidepressant effects may be marketed directly in the future, but require chemo- and enantio-selective chromatographic methods for quality assurance and control. The chromatographic behavior of S-/R-ketamine, S-/R-norketamine, S-/R-dehydronorketamine, and (2R,6R)-/(2S,6S)-hydroxynorketamine in supercritical fluid chromatography (SFC) was investigated computationally and experimentally with the aim of identifying problematic pairs of enantiomers and parameters for chiral resolution. Retention on three different polysaccharide-based chiral stationary phases (Lux Amylose-2, i-Amylose-3, and i-Cellulose-5) provided new information on the significance of halogen atoms as halogen bond donors and hydrogen bond acceptors for enantioselectivity, which could be corroborated in silico by molecular docking studies. Modifiers inversely affected enantioselectivity and retention. Methanol yielded lower run times but superior chiral resolution compared to 2-propanol. Lower temperatures than those conventionally screened did not impair phase homogeneity but improved enantioresolution, at no cost to reproducibility. Thus, sub-ambient temperature subcritical fluid chromatography (SubFC), essentially low-temperature HPLC with subcritical CO2, was applied. The optimization of the SubFC method facilitated the chiral separation of ketamine and its metabolites, which was applied in combination with direct injection and online supercritical fluid extraction to determine the purity of pharmaceutical ketamine formulations for proof of concept.

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Section: Discussionmentioning

confidence: 99%

Subcritical Fluid Chromatography at Sub-Ambient Temperatures for the Chiral Resolution of Ketamine Metabolites with Rapid-Onset Antidepressant Effects

et al. 2019

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“…Supercritical fluid chromatography (SFC) is an alternative technique for separation of chiral compounds and provides several advantages over HPLC. [12][13][14][15] The mobile phase contains a large fraction of carbon dioxide, which has lower viscosity and higher diffusivity than liquid chromatographic solvents. As a consequence, high flow rates can be used without loss of resolution or efficiency and shorter equilibration times are achieved.…”

Section: Several High Performance Liquid Chromatography (Hplc) Methodsmentioning

confidence: 99%

Enantiomeric separation and quantification of R/S‐amphetamine in serum using semi‐automated liquid‐liquid extraction and ultra‐high performance supercritical fluid chromatography‐tandem mass spectrometry

Havnen

Hansen

Spigset

et al. 2020

Drug Testing and Analysis

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The amphetamine molecule contains a chiral center and its enantiomers exhibit differences in pharmacological effects, with the S‐enantiomer mediating most of the central nervous system stimulating activity. The majority of prescribed amphetamine consists of the pure S‐enantiomer, but therapeutic formulations containing the R‐enantiomer in various proportions are also available. Illegal amphetamine remains available mainly as a racemic mixture of the R‐ and S‐enantiomers. To distinguish between legal and illegal consumption of amphetamine a method for enantiomeric separation and quantification of R/S‐amphetamine in serum was developed and validated using ultra‐high performance supercritical fluid chromatography‐tandem mass spectrometry (UHPSFC‐MS/MS). Sample preparation prior to UHPSFC‐MS/MS analysis was performed by a semi‐automated liquid–liquid extraction method. The UHPSFC‐MS/MS method used a Chiralpak AD‐3 column with a mobile phase consisting of CO2 and 0.1% ammonium hydroxide in 2‐propanol/methanol (50/50, v/v). The injection volume was 2 μL and run time was 4 minutes. MS/MS detection was performed with positive electrospray ionization and two multiple reaction monitoring transitions (m/z 136.1 > 119.0 and m/z 136.1 > 91.0). The calibration range was 12.5–1,000 nM for each analyte. The between‐assay relative standard deviations were in the range of 1.3–3.0%. Recovery was 73% and matrix effects ranged from 95 to 100% when corrected with internal standard. After development and validation, the method has been successfully implemented in our laboratory for both separation and quantification of R/S‐amphetamine and has proved to be a reliable and useful tool for distinguishing intake of R‐ and S‐amphetamine in authentic patient samples.

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“…This section describes the recent data present in the literature reported in 2017–2018 and related to the enantiomers separation in food samples. Data on this topic, related to previous years, can be found in previous reviews [23,37].…”

Section: Some Selected Applications To Enantiomers Separation In Fmentioning

confidence: 99%

“…The mobile phase contains carbon dioxide often modified with some organic solvents such as methanol, ethanol, isopropanol, and acetonitrile at relatively low concentrations. In addition to enhancing chiral resolution, other additives, e.g., formic acid (FA), acetic acid (HAc), trifluoracetic acid (TFA), ammonia (NH 3 ), and diethylamine (DEA) have been used [37].…”

Section: Some Selected Applications To Enantiomers Separation In Fmentioning

confidence: 99%

Analysis of Enantiomers in Products of Food Interest

et al. 2019

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The separation of enantiomers has been started in the past and continues to be a topic of great interest in various fields of research, mainly because these compounds could be involved in biological processes such as, for example, those related to human health. Great attention has been devoted to studies for the analysis of enantiomers present in food products in order to assess authenticity and safety. The separation of these compounds can be carried out utilizing analytical techniques such as gas chromatography, high-performance liquid chromatography, supercritical fluid chromatography, and other methods. The separation is performed mainly employing chromatographic columns containing particles modified with chiral selectors (CS). Among the CS used, modified polysaccharides, glycopeptide antibiotics, and cyclodextrins are currently applied.

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SFC for chiral separations in bioanalysis

Cited by 51 publications

References 69 publications

Subcritical Fluid Chromatography at Sub-Ambient Temperatures for the Chiral Resolution of Ketamine Metabolites with Rapid-Onset Antidepressant Effects

Subcritical Fluid Chromatography at Sub-Ambient Temperatures for the Chiral Resolution of Ketamine Metabolites with Rapid-Onset Antidepressant Effects

Enantiomeric separation and quantification of R/S‐amphetamine in serum using semi‐automated liquid‐liquid extraction and ultra‐high performance supercritical fluid chromatography‐tandem mass spectrometry

Analysis of Enantiomers in Products of Food Interest

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