scholarly journals Comparison of Coated and Immobilized Chiral Stationary Phases Based on Amylose tris-[(S)-α-Methylbenzylcarbamate] for the HPLC Enantiomer Separation of α-Lipoic Acid and Its Reduced Form

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1747
Author(s):  
Alessia Rosetti ◽  
Claudio Villani ◽  
Marco Pierini ◽  
Roberto Cirilli
Keyword(s):  
Lipoic Acid ◽  
Stationary Phases ◽  
Antioxidant Properties ◽  
Chiral Stationary Phases ◽  
Reduced Form ◽  
Racemic Mixture ◽  
Column Temperature ◽  
Mobile Phases ◽  
Configuration Assignment

The couple of chiral sulfur compounds α-lipoic acid (ALA)/α-dihydrolipoic acid (DHALA) has attracted considerable attention in recent years owing to its remarkable anti-inflammatory and antioxidant properties. It is well known that the chirality of the C6 plays a key role in determining the biological activity of ALA. The natural occurring (R)-ALA enantiomer is an essential cofactor for key oxidative metabolism enzyme complexes and, after oral administration of the racemic mixture, it shows higher plasma concentration than (S)-ALA. Differently, the in vivo enantioselective action difference between the enantiomers of DHALA has not yet been studied. This lacking is perhaps due to the unavailability of analytical methods capable of determining the enantiomeric composition of biological samples during pharmacokinetic and pharmacodynamic events. In the present work, the direct and baseline enantioresolution of both chiral acids by HPLC on two amylose-derived chiral stationary phases is presented. The proposed chiral enantioselective protocol, therefore, does not require pre- or on-column derivatization. The performance of the coated Chiralpak AS-H CSP and the new immobilized Chiralpak IH-3 CSP, which have the same chiral selector amylose tris-[(S)-α-methylbenzylcarbamate], were compared using conventional normal-phase mobile phases containing ethanol or 2-propanol as alcoholic solvents and a fixed percentage of trifluoroacetic acid. Nonconventional eluents containing dichloromethane, ethyl acetate, and 2-methyltetrahydrofuran as organic cosolvents were applied in the separation of the enantiomers of two carboxylic acids on the immobilized Chiralpak IH-3 CSP. The effect of the column temperature was carefully evaluated in order to improve enantioselectivity. Adequate amounts of enantiomers were isolated by an analytical-size Chiralpak IH-3 column and submitted to chiroptical measurements. The absolute configuration assignment of the isolated enantiomers was determined by a multidisciplinary procedure based on the comparison of the experimental and calculated chiroptical properties.

scholarly journals Stationary phase type and temperature effect on HPLC separation of lactic acid enantiomers

2021 ◽  
Vol 14 (1) ◽  
pp. 60-65
Author(s):  
Laura Jánovová ◽  
Katarína Hroboňová
Keyword(s):  
Lactic Acid ◽  
High Performance ◽  
Stationary Phases ◽  
Chiral Stationary Phases ◽  
Reversed Phase ◽  
Optical Isomers ◽  
Column Temperature ◽  
Retention Factors ◽  
Chromatographic Parameters ◽  
Macrocyclic Antibiotics

Abstract Lactic acid is a biologically important organic acid existing in two enantiomeric forms which are differently metabolized in the human body. In this paper, direct chiral separation of lactic acid by high performance liquid chromatography is presented. Five chiral stationary phases based on macrocyclic antibiotics were used for enantioseparation and chromatographic parameters, such as retention factors, resolution and selectivity factors, were determined under different column temperatures ranging from 5 to 45 °C. Optical isomers of lactic acid were efficiently separated using chiral stationary phases based on teicoplanin (R S = 1.9 ) and ristocetin (R S = 1.7 ) in reversed-phase separation mode at the column temperature of 25 °C.

α-Lipoic Acid and its role on female Reproduction

2021 ◽  
Vol 22 ◽  
Author(s):  
Fiorella Di Nicuolo ◽  
Roberta Castellani ◽  
Carlo Ticconi ◽  
Giovanni Scambia ◽  
Alfredo Pontecorvi ◽  
...  
Keyword(s):  
Lipoic Acid ◽  
Polycystic Ovary ◽  
Antioxidant Properties ◽  
Reduced Form ◽  
Female Reproduction ◽  
Adhesion Protein ◽  
Positive Effects ◽  
Antioxidant Agents ◽  
Tnf Α ◽  
Cytokine Levels

: α-lipoic acid (ALA), also known as thioctic acid, is a biological thiol present in all types of prokaryotic and eukaryotic cells. It has been shown that ALA or its reduced form, DHLA, have several positive effects on human health acting as biological antioxidant, metal chelator and as a detoxifying agent. It is able to reduce oxidation of several antioxidant agents like glutathione, vitamins C and E, and to modulate insulin and NF-kB signaling pathways. ALA’s pharmacological effects are not only related to its antioxidant properties but it shows an anti-inflammatory action. In particular, ALA is able to reduce inflammasome activity, the pro-inflammatory cytokine levels, such as TNF-α, IL-1β, IL-6, IL-18 and IL-17, interferon (INF)-γ as well as the production of Vascular and Intercellular cell adhesion protein (VCAM-1 and ICAM-1). In recent papers, ALA has been indicated as a possible therapeutic approach to several endocrine or inflammatory disorders affecting female reproduction. Aim of the current review was to assess whether ALA has an evidence-based beneficial role on gynecological and obstetrical diseases such as polycystic ovary syndrome (PCOS), endometriosis, and miscarriage.

scholarly journals Pharmacokinetics study of potential anti-CML drug Cyclobentinib (CB1107) by HPLC–MS/MS

2021 ◽  
Vol 3 (1) ◽  
pp. 169-175
Author(s):  
Xinghua Zhao ◽  
◽  
Jiaojiao Zhang ◽  
Yutong Liang ◽  
Jie Li ◽  
...  
Keyword(s):  
Formic Acid ◽  
Mobile Phase ◽  
Time Curve ◽  
Column Temperature ◽  
Mobile Phases ◽  
Ionization Reaction ◽  
Liquid Chromatography Tandem Mass ◽  
Different Doses

Purpose: A simple, sensitive and specific HPLC–MS/MS method was established to analysis the pharmacokinetics of CB1107 in mouses. Methods: A simple, selective, and sensitive high-throughput liquid chromatography-tandem mass spectrometry (LC-MS-MS) method has been developed and validated for quantitative determination of CB1107 in rat serum.Chromatographic separation was achieved on a Zorbax Extend C18 Rapid Resolution HD column (4.6 mm × 50 mm, 1.8 μm). The column temperature was maintained at 35℃ and at flow rate of 0.6 mL/min. Injection volume was 20 μL. The mobile phases consisted of 0.1% formic acid in water (mobile phase A)and 0.1% formic acid in acetonitrile (mobile phase B), and total run time was 30min. MS-MS detection was performed in the selected monitoring mode of electrospray positive ionization reaction. Results: The pharmacokinetic characteristics of CB1107 in mice belong to the two-compartment model.When the doses were 400 mg/kg, 600 mg/kg and 800 mg/kg, corresponding area under the plasma concentration-time curve (AUC) respectively were 20.011±1.24 mg/h/L, 26.778±2.19 mg/h/L, 38.82±1.44 mg/h/L, suggesting that CB1107 have a good absorption in the body.And the AUC of three doses are proportional, indicating that CB1107 conforms to linear pharmacokinetics in vivo. Conclusion: This method was successfully applied to study the pharmacokinetics at three different doses of CB1107 after oral administration in mouses. In this study, the bioactivity mechanism of CB1107, by the pharmacokinetic investigation of CB1107 in vivo.

scholarly journals Amelioration of Metal-Induced Cellular Stress by α-Lipoic Acid and Dihydrolipoic Acid through Antioxidative Effects in PC12 Cells and Caco-2 Cells

2021 ◽  
Vol 18 (4) ◽  
pp. 2126
Author(s):  
Kaniz Fatima Binte Hossain ◽  
Mahmuda Akter ◽  
Md. Mostafizur Rahman ◽  
Md. Tajuddin Sikder ◽  
Md. Shiblur Rahaman ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Lipoic Acid ◽  
Antioxidant Properties ◽  
Membrane Integrity ◽  
Reduced Form ◽  
Metal Exposure ◽  
Related Factor ◽  
Simultaneous Exposure ◽  
Dihydrolipoic Acid ◽  
Cell Membrane Integrity

α-Lipoic acid (ALA) and its reduced form dihydrolipoic acid (DHLA) are endogenous dithiol compounds with significant antioxidant properties, both of which have the potential to detoxify cells. In this study, ALA (250 μM) and DHLA (50 μM) were applied to reduce metal (As, Cd, and Pb)-induced toxicity in PC12 and Caco-2 cells as simultaneous exposure. Both significantly decreased Cd (5 μM)-, As (5 μM)-, and Pb (5 μM)-induced cell death. Subsequently, both ALA and DHLA restored cell membrane integrity and intracellular glutathione (GSH) levels, which were affected by metal-induced toxicity. In addition, DHLA protected PC12 cells from metal-induced DNA damage upon co-exposure to metals. Furthermore, ALA and DHLA upregulated the expression of survival-related proteins mTOR (mammalian target of rapamycin), Akt (protein kinase B), and Nrf2 (nuclear factor erythroid 2-related factor 2) in PC12 cells, which were previously downregulated by metal exposure. In contrast, in Caco-2 cells, upon co-exposure to metals and ALA, Nrf2 was upregulated and cleaved PARP-1 (poly (ADP-ribose) polymerase-1) was downregulated. These findings suggest that ALA and DHLA can counterbalance the toxic effects of metals. The protection of ALA or DHLA against metal toxicity may be largely due to an enhancement of antioxidant defense along with reduced glutathione level, which ultimately reduces the cellular oxidative stress.

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