Published: 2021-06-18

Abstract views: 233   PDF downloads: 144  

Page 187-205

Comparative studies on enantioseparation of New Psychoactive Substances using cyclodextrin-assisted capillary electrophoresis with UV detection

blankpage Eva-Maria Hubner, Patrick Steinkellner, Martin G. Schmid

New psychoactive substances (NPS) count as psychoactive substances, which are slightly modified compared to illicit drugs regarding their chemical structure to circumvent law. Compared to classical drugs such as heroin, cocaine, or amphetamine, they show similar psychoactive effects, however, because of their novelty there is few knowledge about their side effects or toxicity. NPS are available as different chemical substance classes, among them chiral novel derivatives of amphetamine, cathinone, and ketamine. Since in most cases no clinical studies are available about the possibly different effects of the two enantiomers, there is a big demand for enantioseparation method development. Besides high-performance separation techniques such as gas chromatography or HPLC, capillary electrophoresis has turned out to be a powerful alternative for chiral separation development. The addition of chiral additives such as cyclodextrins to the background electrolyte often results in successful attempts. The present study compares the chiral separation power of different previously used non-charged ß-cyclodextrins, among them native ß-cyclodextrin as well as some of its derivatives such as acetyl-, and 2-hydroxypropyl-β-cyclodextrin, with the negatively charged derivatives carboxymethyl-, carboxyethyl- and succinyl-β-cyclodextrin by capillary zone electrophoresis. A total of 136 chiral NPS were investigated with these cyclodextrins, 122 of them were resolved in their enantiomers successfully by means of a simple electrolyte composition consisting of 10 mM aqueous sodium hydrogen phosphate buffer, pH 2.5 and 10 mM of the chiral selector. Furthermore, the presented method turned out to be useful to distinguish between positional isomers and examples for both enantiomer order and positional order for seized samples are given.

Abstract views: 333   PDF downloads: 194  

Page 176-184

Efficacy and mechanism of KRAS G12C PROTAC in inhibiting the proliferation of pancreatic cancer cells

blankpage Shuai Gao, Fangxia Zou, Lixia Zheng, Yunjie Wang, Xinyu Feng, Deshuai Liu, Yutong Mao, Liang Ye, Jingwei Tian

Pancreatic cancer is a rare but highly malignant cancer with few effective treatments available. Targeting cancers bearing specific genetic mutations offers a new approach for cancer therapy. PROTAC (proteolysis-targeting chimeras) is an emerging technique to design targeted therapy and increasing evidence supports its utility. This study examined the in vitro pharmacodynamics and mechanism of PROTAC K-Ras Degrader-1 (PKD-1), a PROTAC molecule, in inhibiting the proliferation of pancreatic cancer cells. We used a pancreatic cancer cell line, MIA PaCa-2 cells, to examined the binding and degradation-promoting capabilities of PKD-1 on KRAS G12C protein and further evaluated the effects of PKD-1 on cell viability, cell cycle and apoptosis. PKD-1 was able to bind to KRAS G12C protein, promoted its degradation for up to 72 h, reduced cell viability, increased cell cycle arrest and promoted cell apoptosis. Mechanistic study found that the efficacy of PKD-1 was at least partially mediated by promoting 26S proteasome degradation process. Combined, these results extended previous findings and support the potential utility of PROTAC molecules such as PKD-1 as a new treatment strategy against pancreatic cancer.

Abstract views: 630   PDF downloads: 373  

Page 169-175

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

blankpage Xinghua Zhao, Jiaojiao Zhang, Yutong Liang, Jie Li, Shi Ding, Yang Wang, Ye Chen, Ju Liu

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.

Abstract views: 270   PDF downloads: 119  

Pages 185-186

Pharmacy, the continuously expanding field of science

blankpage Pál Perjési

Originating from the traditional herbal formulations, nowadays, Pharmacy covers all the disciplines focusing on the behavior of complex pharmaceutical forms, drug-releasing systems, and active compounds in the human body. Masters of pharmaceutical sciences must know the basics of pharmaceutical chemistry, pharmaceutical technology, biotechnology, biology, physiology, pharmacology, and toxicology.