A kind of high performance liquid chromatography detection method of sirolimus

A high-performance liquid chromatography and detection method technology, applied in the field of drug analysis, can solve the problems of being unfavorable for the detection of weakly polar and strongly retained impurities, unfavorable for the control of ring-opening degradation products, and not adjusting pH, etc., and achieves good separation and accuracy. High and improved separation effect

Active Publication Date: 2019-09-17
SHANGHAI INST FOR FOOD & DRUG CONTROL
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  • Abstract
  • Description
  • Claims
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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

Method used

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  • A kind of high performance liquid chromatography detection method of sirolimus
  • A kind of high performance liquid chromatography detection method of sirolimus
  • A kind of high performance liquid chromatography detection method of sirolimus

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] HPLC detection

[0049] Preparation of sirolimus sample solution: take sirolimus bulk drug, dissolve it with anhydrous acetonitrile, and prepare a 1 mg / mL solution; take 20 μL sirolimus sample solution, inject sample, Qualitative and quantitative analysis of main components, related substances and impurities;

[0050] Wherein, mobile phase A is 20mM ammonium formate buffer solution (i.e. ammonium formate buffer system, pH is about 3.8), mobile phase B is acetonitrile-methyl tert-butyl ether (volume ratio 99:1, the percentage below also represents volume percentage), wherein methyl tert-butyl ether is used as a modifier; the linear gradient elution conditions are: 0~18min: 43%A, 57%B; 18~25min: 29%A, 71%B; 25~33min: 100% B; 33~43min: 100%B (maintain for 10 minutes); after 43min: 43%A, 57%B;

[0051] See Figure 1~4 . exist Figure 1~4 Among them, chromatographic peak 1 is sirolimus, 2 is sirolimus tautomer C, and the rest of the chromatographic peaks are the main impu...

Embodiment 2

[0059] HPLC detection

[0060] Preparation of sirolimus sample solution: take sirolimus capsules from enterprise B, dissolve them in anhydrous acetonitrile, and prepare a 0.5 mg / mL solution; take 20 μL sirolimus sample solution, inject the sample, and Qualitative and quantitative analysis of main components, related substances and impurities in Moss capsules;

[0061] Wherein, mobile phase A is 20mM ammonium formate buffer solution (i.e. ammonium formate buffer system, pH is about 3.8), mobile phase B is acetonitrile-methyl tert-butyl ether (volume ratio 99:1, the percentage below also represents volume percentage), wherein methyl tert-butyl ether is used as a modifier; the linear gradient elution conditions are: 0~18min: 43%A, 57%B; 18~25min: 29%A, 71%B; 25~33min: 100% B; 33~43min: 100%B (maintain for 10 minutes); after 43min: 43%A, 57%B;

[0062] See the test results Figure 5 , wherein: chromatographic peak 1 is sirolimus, 2 is sirolimus tautomer C, and the remaining chr...

Embodiment 3

[0066] HPLC detection

[0067] Preparation of sirolimus sample solution: take the sirolimus raw material drug from enterprise A, dissolve it in anhydrous acetonitrile, and prepare a 1 mg / mL solution; take 20 μL sirolimus sample solution, inject it, and Qualitative and quantitative analysis of main components, related substances and impurities in Moss capsules;

[0068] Among them, mobile phase A is 20mM ammonium formate buffer solution (i.e. ammonium formate buffer system, pH is about 3.8), mobile phase B is acetonitrile-tetrahydrofuran (volume ratio 97:3), wherein tetrahydrofuran is used as modifier; linear gradient elution The conditions are: 0-20min: 44%A, 56%B; 20-30min: 57%A, 43%B; 30-40min: 100%B; 40-50min: 100%B (maintain for 10 minutes); after 50min : 44% A, 56% B;

[0069] See the test results Figure 9 , wherein: chromatographic peak 1 is sirolimus, 2 is sirolimus tautomer C, and the rest of the chromatographic peaks are main impurity peaks: 3 is prolyl sirolimus,...

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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...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): G01N30/89G01N30/34
Inventor 赵敬丹缪天瑶秦峰刘浩
Owner SHANGHAI INST FOR FOOD & DRUG CONTROL
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