胃内容物中甲卡西酮LC-MS/MS检验方法研究

目的:建立胃内容物中甲卡西酮及其代谢物卡西酮的LC-MS/MS检验方法。方法:以双苯戊二氨酯(SKF525A)为内标,Column Eclipse Plus C18色谱柱(1.8μm, 100 mm×3 mm)为固定相,流动相为0.1%甲酸水溶液和乙腈,梯度洗脱,流速为0.3m L/min,进样量为1μL。通过电喷雾离子源(ESI),利用正离子多反应监测模式(MRM)进行检测。结果:胃内容物中甲卡西酮检验方法线性范围为1-5000 ng/g,标准曲线方程Y=0.026X+0.4501(R2=0.9998),检出限为0.5 ng/g,定量限为1.0 ng/g;卡西酮的检验方法线性范围为2-5000 ng/g,标准曲线方程Y=0.0099X+0.1576(R2=0.9997),检出限为1.0 ng/g,定量限为2.0 ng/g。结论:该方法操作简便,检测灵敏度较高,可用于甲卡西酮中毒案件胃内容物中甲卡西酮及其代谢物卡西酮的检验。     

Cathinone: An alkaloid of Catha edulis (Khat) exacerbated hyperglycemia in diabetes-induced rats

Cathinone, the main bioactive alkaloid of Catha edulis (khat), slightly increased the blood sugar levels of healthy animals, while its effect on blood sugar levels of diabetic animals has not yet been reported. This study investigated the in vitro inhibition of cathinone on α-amylase and α-glucosidase as well as its in vivo glycemic effects in diabetes-induced rats. Rats were fed on a high fat diet for five weeks, which then intraperitoneally injected with streptozotocin (30 mg/kg). Diabetic rats were distributed randomly into diabetic control (DC, n = 5), 10 mg/kg glibenclamide-treated group (DG, n = 5), and 1.6 mg/kg cathinone-treated group (CAD, n = 5). Additional healthy untreated rats (n = 5) served as a nondiabetic negative control group. Throughout the experiment, fasting blood sugar (FBS), caloric intake and body weight were recorded weekly. By the 28th day of treatment, rats were euthanized to obtain blood samples and pancreases. The results demonstrated that cathinone exerted a significantly less potent in vitro inhibition than α-acarbose against α-amylase and α-glucosidase. As compared to diabetic control group, cathinone significantly increased FBS of diabetic rats, while insulin levels of diabetic rats significantly decreased. In conclusion, cathinone was unable to induce a substantial in vitro inhibition on α-amylase and α-glucosidase, while it exacerbated the hyperglycemia of diabetes-induced rats.     

Behavioral pharmacology of designer cathinones: A review of the preclinical literature

“Bath salts” is one street name for a family of synthetic cathinones that display pharmacological effects resembling cocaine and commonly abused amphetamines. Despite extensive legislation aimed at the criminalization of bath salts, several designer cathinones are gaining a foothold in the illicit drug scene; for example, in the United Kingdom, mephedrone (4-methylmethcathinone, MEPH) is highly popular among drug abusers whereas, in the United States, MDPV (methylenedioxypyrovalerone) and methylone are highly prevalent. To date, knowledge about the hazards of designer cathinones is based mostly on hospital reports and anecdotal evidence derived from online surveys. Despite the paucity of preclinical studies directed toward designer cathinones, a number of invaluable findings arising from those studies are enabling scientists to develop their neuropharmacological profiles. Despite their commonalities in chemical structures, synthetic cathinones possess distinct neuropharmacological profiles and produce different behavioral effects, including unique effects on locomotor activity, learning, anxiety, thermoregulation, and abuse liability. The present review will discuss the behavioral effects of MEPH, MDPV, and methylone and compare those effects to established psychostimulant drugs. The rise in the use of designer cathinones in the United States and abroad justifies further investigations into these compounds, both for a greater understanding of the danger that “bath salts” pose to the public, and to provide insight into replacement cathinones as they emerge onto the market.     

Emergence and properties of spice and bath salts: A medicinal chemistry perspective

Over the past five years the number of internet sites advertising “legal highs” has literally exploded, as have user reports of experiences (both pleasurable and frightening) with these substances and the number of emergency room visits by users. Although the majority of these “legal highs” have been described as bath salts and herbal extracts, most contain neither plant derived compounds nor components of personal hygiene products. So-called “bath salts” largely contain synthetic analogs of the natural compound Khat; spice-related materials, claimed to be “legal marijuana,” are mostly synthetic analogs of cannabinoid receptor ligands that were developed as research tools. This review describes the emergence and properties of these two groups of “legal highs” from a medicinal chemist's perspective.     

Phylogeny of the Celastreae (Celastraceae) and the relationships of Catha edulis (qat) inferred from morphological characters and nuclear and plastid genes

The phylogeny of Celastraceae tribe Celastreae, which includes about 350 species of trees and shrubs in 15 genera, was inferred in a simultaneous analysis of morphological characters together with nuclear (ITS and 26S rDNA) and plastid (matK, trnL-F) genes. A strong correlation was found between the geography of the species sampled and their inferred relationships. Species of Maytenus and Gymnosporia from different regions were resolved as polyphyletic groups. Maytenus was resolved in three lineages (New World, African, and Austral-Pacific), while Gymnosporia was resolved in two lineages (New World and Old World). Putterlickia was resolved as nested within the Old World Gymnosporia. Catha edulis (qat, khat) was resolved as sister to the clade of Allocassine, Cassine, Lauridia, and Maurocenia. Gymnosporia cassinoides, which is reportedly chewed as a stimulant in the Canary Islands, was resolved as a derived member of Gymnosporia and is more closely related to Lydenburgia and Putterlickia than it is to Catha. Therefore, all eight of these genera are candidates for containing cathinone- and/or cathine-related alkaloids.     

The psychostimulant drug khat (Catha edulis): A mini-review

Khat (Catha edulis Forsk) is a shrub native to the Horn of Africa and the Middle East. The leaves of this small tree are chewed by millions worldwide as a mild, amphetamine-like psychostimulant drug. Whilst khat has enjoyed grey-area legality in many countries including the United Kingdom that otherwise prohibit the use of recreational drugs, recent years have seen the appearance of new legislation to control its production, importation and consumption. This mini-review will consolidate what is known about the pharmacology, chemistry, and effects on health of khat to provide a brief synopsis of the properties of this plant stimulant.