| Steroids are a class of tetracyclic aliphatic hydrocarbon compounds with the cyclopentanoperhy drophenanthrene structure,which exist widely in human and animals and play an important role in metabolism,internal environmental stability,the regulation of growth and reproductive behavior.In general,steroids have a normal range in human body,it will leads to endocrine dysfunction and a variety of diseases when out of the range.Therefore,determination of endogenous steroid hormones is of great significance in the prevention and treatment of diseases.As a special commodity,the quality of medicine is closely related to people’s health and life safety.Therefore,the quality control must be carried out in all periods of the drug research and development,production,circulation and storage.The study of drug impurities is an important part in drug quality control.The analysis and detection of the related impurities in the drug provides the basis for the optimization of the production process and quality control.The review of this paper states the detection methods of steroid hormones in domestic and overseas after a brief introduction to the types and function of steroid hormones.Secondly,we describe the classification and the source of the impurities of the drug,especially the application of high performance liquid chromatography mass spectrometry(HPLC-MS)in the analysis of impurities.The experiment is divided into two parts,the derivatization of steroid hormones was selected and the derivatization reaction conditions and mass spectrometry conditions baesd on ESI-MS had been optimized in the first part;in the other part,the related impurities of tebipenem intermediate side chain and nuclear parent(MAP)were analysed and detected,the analytical conditions were optimized and several possible impurities were identified by mass spectrometry data and fragmentation information.The specific research contents and results include the following two aspects:Firstly,we had been selected 10 kinds of hydrazine compounds which synthesized by our school of pharmacy to react with testosterone based on ESI-MS,while the results were not very good.Then,seven kinds of hydrazine compounds with relatively small molecular weight were reacted with testosterone based on ESI-MS.The results showed that salicylic hydrazide derivative was best.With salicylhydrazide as derivatization reagent who reacted with progesterone,pregnenolone,estrone,dehydroepiandrosterone and dihydrotestosterone.The solvent,temperature,time,pHand the amount of salicylhydrazone were optimized.The reaction conditions of salicylhydrazide and steroid hormones were simple and efficiency.With the rapid and sensitive method that it can be used as a derivatization reagent for the detection of steroid hormones.Secondly,the related impurities of tebipenem intermediate side chain and nuclear parent(MAP)were analysed and detected,the optimum separation conditions based on HPLC had been determined.The mobile phase and elution program were optimized,the impurities of drug were analysed efficiently within 20 min.According to the information of synthetic process,HPLC retention time,mass spectrogram of liquid chromatography and fragmentation information,the possible structure of impurities was speculated,the fragmentation pathway of impurities were also analyzed.With our study that we can provide the reference for tebipenem drug development and quality control. |
