Method for separating and determining bortezomib chiral isomers through high-performance liquid chromatography

Abstract

The invention provides a bortezomib isomer separating and determining method. The bortezomib isomer separating and determining method is characterized in that a chiral chromatographic column is adopted, the surface of the stationary phase silica gel of the chiral chromatographic column is coated with amylose-tris(3, 5-xylyl carbamate), a mobile phase is a combination of a mobile phase A and a mobile phase B, the mobile phase A is a normal hexane solution containing 0.1% of trifluoroacetic acid, the mobile B is an absolute methanol / isopropanol solution, the ratio of absolute methanol to isopropanol is 1: 1, the flow velocity is 0.1-0.7ml / min, and the column temperature is 25-40 DEG C. By adopting the method, bortezomib and three chiral isomers thereof can be effectively separated, the degree of separation reaches 1.7-4.2, peak shapes are good, and the number of theoretical plates is high. The bortezomib isomer separating and determining method can be used for the control on the production quality of bortezomib raw drugs.

Description

technical field [0001] The invention relates to the field of drug analysis, in particular to a method for separating and measuring isomers of the anticancer drug bortezomib. Background technique [0002] Bortezomib is a synthetic dipeptide borate, which is a reversible proteasome inhibitor. It can selectively bind to threonine in the active site of proteasome and inhibit the chymotrypsin / proteasome 26S subunit. Trypsin activity. At the same time, it can also improve the anti-tumor effect of other anti-tumor drugs, and present synergistic or sensitizing effects when used in combination with many drugs, rather than purely additive effects. The anti-myeloma effect is achieved through a new mechanism. Clinical studies at home and abroad have shown that bortezomib monotherapy and combined chemotherapy regimens with conventional chemotherapy drugs have good curative effects on initial treatment and relapsed and refractory MM patients. It is considered a breakthrough therapy for...

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Problems solved by technology

[0007] During the quality control of bortezomib, it is necessary to strictly control the content of the isomers. Due to the closeness of the properties between the isomers, it is difficult to separate and measure the content of the isomers by using the prior art high-performance liquid chromatography analysis method for bortezomib.

The liquid chromatography method disclosed in the document "Development and Validation of a Stability Indicating LC Method for the Assay and Related Substances Determination of a Proteasome Inhibitor Bortezomib" on the separation of bortezomib and its nine related impurities, which contains the above-mentioned bortezomib The two chiral isomers of BIO1 and BIO2, but BIO3 is not in the scope of this literature review, the method uses RP18 chromatographic column, mobile phase A: acetonitrile / water (0.1% formic acid), mobile phase B: methanol / water (0.1% formic acid), the detection wavelength is 270nm, the flow rate is 1.0ml / min, the column temperature is 35°C, and the injection volume is 20ul. For the separation of the chiral isomers of bortezomib, only the overlapping peaks of BIO1 and BIO2 can be combined with Bortezomib was separated, and the BIO3 peak overlapped with the bortezomib peak, so the method failed to separate bortezomib and the remaining three chiral isomers

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