A kind of high performance liquid chromatography detection method of sirolimus

Abstract

The invention provides a high-performance liquid chromatographic detection method of sirolimus, which takes anhydrous acetonitrile as a solvent and acetonitrile and a buffer salt solution as a mobile phase, and a modifier is selectively added to be capable of effectively improving separation of prolyl sirolimus, a sirolimus tautomer A, demethylated sirolimus and sirolimus main peak. The high-performance liquid chromatographic detection method of the sirolimus is easy and simple to operate and good in specificity; a sample solution is good in stability; the sirolimus, the tautomer, a homolog and a technology byproduct (such as the prolyl sirolimus and the demethylated sirolimus), a ring-opening degradation product (such as rapamycin) and the like can be effectively separated; the quantity of detected impurities is larger; related chromatographic peaks (the technology byproduct, the degradation product and the like) are separated well; the accuracy and repetitiveness are high; the method can effectively overcome defects in the prior art, and further effectively control product quality of a bulk drug and a preparation of the sirolimus, and can be also used for evaluating a production technology of the sirolimus.

Description

technical field [0001] The invention belongs to the technical field of drug analysis, and in particular relates to a high performance liquid chromatography detection method for sirolimus. Background technique [0002] Sirolimus, also known as rapamycin, is a lipophilic nitrogen-containing 36-membered macrolide immunosuppressant. In 1975, Vezina et al. from Ayerst Laboratory in Canada obtained it for the first time from the fermentation broth of Streptomyes hygroscopicus isolated from the soil samples of Easler Island in the Pacific Ocean. In 1977, sirolimus was found to have an immunosuppressive effect, and in 1989, sirolimus was used as a new drug for the treatment of organ transplant rejection. In October 1999, sirolimus oral solution developed by Wyeth Pharmaceuticals was first launched in the United States. Since then, 1mg tablets have also been launched in the United States. [0003] Domestic sirolimus products mainly include sirolimus raw materials, sirolimus capsule...

AI Technical Summary

Problems solved by technology

[0005] (2) The composition of the mobile phase is an organic solvent-water mixture. The mobile phase system does not adjust the pH, which is not conducive to the control of ring-opening degradation products such as broken rapamycin. Under this premise, it is very unfavorable to use isocratic elution. Facilitate the detection of weakly polar and strongly retained impurities;

[0006] (3) Regarding the control of impurities in related substances, there are 2 prior art mentions of the known impurity desmethyl sirolimus, and 1 prior art mentions desmethyl sirolimus and ring-opening degradation conversion products However, there is an obvious error in its conclusion, which is because: in the detection process of sirolimus, the ring-opening degradation transformation product has been confirmed as broken rapamycin and sirolimus homologues and sirolimus Mixture of isomers of limus, the known impurity desmethyl sirolimus has been identified as prolyl sirolimus

[0008] In summary, there are many defects and deficiencies in the prior art in terms of effective and controllable quality control for sirolimus API and its preparations

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