Dissertation > Medicine, health > Pharmacy > Pharmacopoeia Codex ( formulary ),drug identification > Drug identification > Determination of drug content

Identification and synthesis of trace impurities ondansetron four kinds of chemical drugs

Author GaoHu
Tutor WuSong
School Beijing Union Medical College
Course Medicinal Chemistry
Keywords ondansetron amlodipine gestodene levonorgestrel impurity synthesis
CLC R927.2
Type Master's thesis
Year 2012
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The medicine impurity research is a key part throughout the process of new and generic drug research. And it plays a very important role in insuring high quality of medicine.In order to solve the problem of no impurity standards’source, seven traceimpurities including ondansetron impurity B, amlodipine impurity D, two impurities of gestodene and three impurities of levonorgestrel were synthesized through simple and convenient routes.Ondansetron impurity B, an impurity in the preparation of ondansetron hydrochloride, was synthesized from4,4’-diaminodiphenylmethane by diazotization, reduction, condensation with1,3-cyclohexanedione, Fischer cyclization, methylation, aldol condensation with paraformaldehyde and Michael addition with2-methylimidazole with a total yield of2.5%.Amlodipine impurity D was an oxidizied impurity of amlodipine. In this thesis, the acetate of amlodipine impurity D was synthesized from amlodipine by lead tetraacetate oxidation, salt formation and recrystallization from isopropyl ether with a yield of56.7%.ZP003-S008and ZP003-S009were two traceimprities isolated from crude gestodene. ZP003-S009was synthesized from15a-hydroxy-18-methylestra-4-ene-3,17-dione by ketalization, ethynylation and hydrolysis with a yield of12.1%. ZP003-S008was synthesized from ZP003-S009by acetylation with a yield of72.9%.ZP001-S020, ZP001-S021and ZP001-S022were three traceimprities isolated from crude levonorgestrel. ZP001-S021and ZP001-S022were synthesized from levonorgestrel by hemi-ketalization, oxidization with meta-chloroperoxybenzoic acid sodium salt with a yield of9.1%and27.2%respectively. ZP001-S020was synthesized from ZP001-S021and ZP001-S022by oxidization with Pyridinium chlorochromate with a yield of40.0%.All the target compounds were confirmed by MS and1D/2D NMR. The purities of the compounds were tested by HPLC and all of them were above98%.

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