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

A technology of high performance liquid chromatography and chiral isomers, which is applied in the field of separation and determination of anticancer drug bortezomib isomers, can solve the problem of unrealized separation of chiral isomers of bortezomib and difficult separation and determination of isomers. Construct content and other issues

Inactive Publication Date: 2014-02-26
深圳万乐药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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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

Method used

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

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Experimental program
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Embodiment 1

[0042] Instrument: SHIMAZU LC-20AT high performance liquid chromatography, SPD-10AVP ultraviolet detector, CTO-10ASVP column thermostat;

[0043] Chromatographic column: Chiralomix SA chromatographic column (5μm, 250mm×4.6mm);

[0044] Mobile phase: n-hexane (0.1% trifluoroacetic acid): (anhydrous methanol: isopropanol=1:1)=90:10;

[0045] Column temperature: 40°C;

[0046] Flow rate: 0.3ml / min;

[0047] Detection wavelength: 270nm;

[0048] Preparation of positioning solution 1: accurately weigh an appropriate amount of bortezomib isomer BIO1, add anhydrous methanol to dissolve and make 10 μg / ml; preparation of positioning solution 2: accurately weigh an appropriate amount of bortezomib isomer BIO2, add Dissolve in water and methanol to make 10 μg / ml; preparation of positioning solution 3: accurately weigh an appropriate amount of bortezomib isomer BIO3, add anhydrous methanol to dissolve and make 10 μg / ml; preparation of system suitability solution: take bortezomib Rice ...

Embodiment 2

[0051] The determination of isomer in the embodiment dibortezomib crude drug

[0052] Chromatographic conditions and system suitability test using chiral chromatographic column (Chiralpak AD-H, 4.6 × 250mm); with n-hexane (0.1% trifluoroacetic acid): (isopropanol: anhydrous methanol = 1: 1)) = 90 : 10 is the mobile phase; the flow rate is 0.3ml / min; the column temperature is 40°C; the detection wavelength is 270nm; take bortezomib reference substance and isomer reference substance, add an appropriate amount of anhydrous methanol to dissolve, add mobile phase to dilute and prepare each 1ml of the mixed solution containing 10μg is used as the system suitability test solution. Accurately measure 5μl of this solution and inject it into the liquid chromatograph, and record the chromatogram (attached Figure 5 ), according to the order of BIO3, bortezomib, BIO1, BIO2 peaks, the system suitability test results:

[0053] project

[0054] Determination method Take about 50 ...

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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...

Claims

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Application Information

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IPC IPC(8): G01N30/36
Inventor 赵学政张莉袁庆宝玉荣王长平
Owner 深圳万乐药业有限公司
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