81496-81-3Relevant articles and documents
Development and validation of a liquid chromatography and ion spray tandem mass spectrometry method for the quantification of artesunate, artemether and their major metabolites dihydroartemisinin and dihydroartemisinin-glucuronide in sheep plasma
Duthaler, Urs,Keiser, Jennifer,Huwyler, Joerg
, p. 172 - 181 (2011)
Recently, promising fasciocidal activities of artesunate and artemether were described in rats and sheep. Therefore, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to quantify artesunate, artemether and their metabolites dihydroartemisinin and dihydroartemisinin-glucuronide in sheep plasma. Protein precipitation with methanol was used for sample workup. Reversed-phase high-performance liquid chromatography (HPLC) was performed using an Atlantis C18 analytical column with a mobile phase gradient system of ammonium formate and acetonitrile. The analytes were detected by MS/MS using selected reaction monitoring (SRM) with electrospray ionisation in the positive mode (transition m/z 267.4 → 163.0). The analytical range for dihydroartemisinin, dihydroartemisinin-glucuronide and artesunate was 10-1000 ng/ml and for artemether 90-3000 ng/ml with a lower limit of quantification of 10 and 90 ng/ml, respectively. Inter- and intra-day accuracy and precision deviations were 10%. Consistent relative recoveries (60-80%) were observed over the investigated calibration range for all analytes. All analytes were stable in the autosampler for at least 30 h (6 °C) and after three freeze and thaw cycles. The validation results demonstrated that the LC-MS/MS method is precise, accurate and selective and can be used for the determination of the artemisinins in sheep plasma. The method was applied successfully to determine the pharmacokinetic parameters of artesunate and its metabolites in plasma of intramuscularly treated sheep.
Synthesis and cytotoxicity studies of artemisinin derivatives containing lipophilic alkyl carbon chains
Liu, Yungen,Wong, Vincent Kam-Wai,Ko, Ben Chi-Bun,Wong, Man-Kin,Che, Chi-Ming
, p. 1561 - 1564 (2005)
(Chemical Equation Presented) Cytotoxic artemisinin derivatives have been synthesized by a modular approach of "artemisinin + linker + lipophilic alkyl carbon chain". A strong correlation between the length of the carbon chains and the cytotoxicities against human hepatocellular carcinoma (HepG2) was revealed. Notably, compared with artemisinin (IC50 = 97 μM), up to 200-fold more potent cytotoxicity (IC50 = 0.46 μM) could be achieved by attachment of a C14H29 carbon chain to artemisinin via an amide linker.
Method for preparing dihydroartemisinin crude drug by single process
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Paragraph 0046-0088, (2019/08/03)
The invention belongs to the technical field of production of dihydroartemisinin crude drugs, and particularly relates to a method for preparing a dihydroartemisinin crude drug through a single process. The method comprises the following steps: S1, dissolving artemisinin in a non-protonic solvent; S2, sequentially adding a phase transfer catalyst and a reducing agent, and performing reduction reaction on the artemisinin; S3, adjusting the pH value of the reaction system obtained in step the S2 to 5-7 with acid liquor, adding water, stirring, performing liquid separating, extracting a water phase obtained by the liquid separating with the same non-protonic solvent as in the step S1, and finally combining an organic phase obtained by the extracting with an organic phase obtained by liquid separating, washing with water, and drying; and S4, precipitating crystals from the dried organic phase obtained by the S3 in a crystallization-filter pressing-drying three-in-one crystallization device, then concentrating, filter-pressing and drying to obtain a dihydroartemisinin refined product. The invention provides the method for preparing the high-purity dihydroartemisinin crude drug, and thepurity and the yield of the dihydroartemisinin prepared by the method can reach more than 99%.
A process for preparing β - pedic ether process
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Paragraph 0029-0030, (2018/04/21)
The invention discloses a technology for preparing beta-artemether. The technology comprises the following steps: reducing an initial raw material artemisinin in the presence of a reducing agent to generate dihydroartemisinin, and carrying out an etherification reaction on dihydroartemisinin and trimethyl orthoacetate in the presence of a catalyst to prepare beta-artemether. Experiments prove that the technology allows the content of alpha-artemether generated in the methyl etherification reaction to be smaller than 3%, the HPLC purity of the obtained beta-artemether to be improved to above 99.8%, the content of single impurities to be smaller than 0.1% respectively and the quality of the above product to accord with requirements of United States Pharmacopeia; and the total mole yield of the product by artemisinin can reach 95% or above. The technology can avoid tedious intermediate processing links in the prior art, realizes simple-operation low-cost high-yield preparation of highly pure beta-artemether, accords with industrial production demands of beta-artemether, and has industrial application values.
Facile stoichiometric reductions in flow: An example of artemisinin
Fan, Xiaolei,Sans, Victor,Yaseneva, Polina,Plaza, Dorota D.,Williams, Jonathan,Lapkin, Alexei
experimental part, p. 1039 - 1042 (2012/08/07)
Stoichiometric reduction of artemisinin to dihydroartemisinin (DHA) has been successfully transferred from batch to continuous flow conditions with a significant increase in productivity and an increase in selectivity. The DHA space-time-yield of up to 1.6 kg h-1 L-1 was attained which represents a 42 times increase in throughput compared to that of conventional batch process.
