CN-122017080-A - GC-MS method for determining contents of camphor, isoborneol and L-borneol in concentrate solution for edaravone right camphol injection

CN122017080ACN 122017080 ACN122017080 ACN 122017080ACN-122017080-A

Abstract

The invention discloses a GC-MS method for determining the contents of camphor, isoborneol and L-borneol in a concentrate solution for edaravone right camphol injection, and belongs to the technical field of medicine analysis. The method adopts a gas chromatography-mass spectrometry technology to prepare a sample solution, an impurity stock solution, a reference substance solution and a system applicability solution, a capillary column taking beta cyclodextrin as a fixed liquid is taken as a chromatographic column, the reference substance solution and the sample solution are respectively and precisely measured and directly injected, the chromatograms are recorded, the contents of camphor, isoborneol and L-borneol are calculated according to an external standard method by peak areas, and impurities in the edaravone right-camphol concentrated solution comprise camphor, isoborneol and L-borneol. The method has the advantages of strong specificity, high sensitivity, good accuracy, good stability and strong durability, can effectively control the quality of the concentrate solution for the edaravone right camphene injection, and ensures the medication safety.

Inventors

CAO YUANMIN
ZHANG GUOWEN
ZHAO JIE
JIA ZHIXIANG
NIU BEN

Assignees

江苏联环药业股份有限公司

Dates

Publication Date: 20260512
Application Date: 20260320

Claims (10)

The GC-MS method is used for determining the contents of camphor, isoborneol and L-borneol in the concentrate solution for edaravone right camphol injection, and is characterized by comprising the following steps of: 1) Preparing a sample solution, an impurity stock solution, a reference substance solution and a system applicability solution; 2) Setting chromatographic conditions, namely taking a capillary column with beta cyclodextrin as a fixed liquid as a chromatographic column, taking a mass spectrum detector as a detector, taking an ion source as an electron bombardment source, taking the ion source temperature as 260 ℃ and the quadrupole temperature as 180 ℃, delaying a solvent for 10 minutes, selecting ion monitoring, determining that the quantitative ion is 95 and the electron energy is 70eV; 3) Respectively precisely measuring the reference substance solution and the sample solution, directly sampling, recording the chromatograms, and calculating the contents of camphor, isoborneol and L-borneol according to the peak area by an external standard method; Impurities in the edaravone right camphol concentrated solution for injection comprise camphor, isoborneol and levoborneol.
2. The GC-MS method for determining the content of camphor, isoborneol and L-borneol in the concentrate solution for edaravone right-camphol injection according to claim 1 is characterized in that in the step 1), the preparation process of the sample solution is that 5ml of the concentrate solution for edaravone right-camphol injection is precisely measured, and the sample solution is put into a 10ml measuring flask, dissolved and diluted to a scale by adding absolute ethyl alcohol, and uniformly shaken to be used as the sample solution.
3. The method for determining the content of camphor, isoborneol and L-borneol in the concentrate solution for edaravone right camphol injection according to claim 1 is characterized in that in the step 1), the impurity stock solution (1) is prepared by taking about 12.5mg of L-borneol reference substance, precisely weighing, placing in a 25ml measuring flask, adding 50% ethanol for dissolution and dilution to scale, shaking, precisely weighing 5ml, placing in a 50ml measuring flask, diluting to scale with 50% ethanol, shaking, preparing a solution containing about 50 mug of L-borneol in each 1ml as an impurity stock solution (1), and the impurity stock solution (2) is prepared by taking about 10mg of camphor reference substance and about 15mg of isoborneol reference substance, precisely weighing, placing in the same 100ml measuring flask, adding 50% ethanol for dissolution and dilution to scale, shaking, precisely weighing 5ml, placing in a 50ml measuring flask, diluting to scale with 50% ethanol, shaking, and preparing a mixed solution containing about 10 mug of camphor and about 15 mug of isoborneol in each 1ml as an impurity stock solution (2).
4. The GC-MS method for determining the content of camphor, isoborneol and L-borneol in the concentrate solution for edaravone right camphol injection according to claim 1 is characterized in that in the step 1), the preparation process of the reference solution is that 1ml of each impurity stock solution (1) and 1ml of each impurity stock solution (2) are precisely measured, the mixture solution is put into a 20ml measuring flask, diluted to scale with 50% ethanol and shaken uniformly, and the mixed solution containing 0.5 mug of camphor, 0.75 mug of isoborneol and 2.5 mug of L-borneol in each 1ml is prepared as the reference solution.
5. The GC-MS method for determining the content of camphor, isoborneol and L-borneol in the concentrate solution for edaravone right-camphol injection according to claim 1 is characterized in that in the step 1), the preparation process of the system applicability solution comprises the steps of precisely measuring 5ml of the concentrate solution sample for edaravone right-camphol injection, placing the sample into a 10ml measuring flask, adding 0.5ml of an impurity stock solution (1), diluting to a scale with absolute ethyl alcohol, and shaking uniformly to obtain the system applicability solution.
6. The GC-MS method for determining the content of camphor, isoborneol and L-borneol in the concentrate solution for edaravone right camphol injection according to claim 1 is characterized in that in the step 2), the initial temperature is 45-70 ℃.
7. The GC-MS method for determining the content of camphor, isoborneol and L-borneol in the concentrate solution for edaravone right camphol injection according to claim 1 is characterized in that in the step 2), the temperature of a sample inlet is 295-305 ℃.
8. The GC-MS method for determining the content of camphor, isoborneol and L-borneol in the concentrate solution for edaravone right camphol injection according to claim 1 is characterized in that in the step 2), carrier gas is high-purity helium, and the flow rate of the carrier gas is 1.0-2.2 ml/min.
9. The GC-MS method for determining the content of camphor, isoborneol and L-borneol in the concentrate solution for edaravone right camphol injection according to claim 1 is characterized in that in the step 2), the split ratio is 5:1, and the sample injection amount is 1 μl.
10. The GC-MS method for determining the content of camphor, isoborneol and L-borneol in the concentrate solution for edaravone right camphol injection according to claim 1 is characterized in that in the step 3), the limitation is judged, and if the content of camphor in a sample is less than or equal to 0.2%, the content of isoborneol is less than or equal to 0.3% and the content of L-borneol is less than or equal to 1.0%, the sample is judged to meet the quality requirement.

Description

GC-MS method for determining contents of camphor, isoborneol and L-borneol in concentrate solution for edaravone right camphol injection Technical Field The invention belongs to the technical field of medicine analysis, and particularly relates to a method for determining the contents of camphor, isoborneol and L-borneol in a concentrate solution for edaravone right camphol injection by a GC-MS method. Background The edaravone right camphol injection concentrated solution is a key medicament for clinically treating acute ischemic cerebral apoplexy, and the main component of the edaravone right camphol injection concentrated solution can remove free radicals, and the right camphol can improve brain microcirculation, and the two cooperatively exert curative effects. However, during the production, storage and transportation of the medicine, impurities such as camphor, isoborneol, and levoborneol may be generated due to the introduction of raw materials, degradation reaction, and the like. Wherein, camphor has potential neurotoxicity, and isoborneol and levoborneol influence the stability and curative effect of the medicine, so that the establishment of an accurate, reliable and sensitive detection method is important to strictly limit control of the three impurities. Currently, methods for detecting volatile impurities in drugs mainly include Gas Chromatography (GC), gas chromatography-mass spectrometry (GC-MS), and the like. The gas chromatography has the advantages of high separation efficiency, high analysis speed and the like, but is difficult to effectively separate isoborneol and levorotatory borneol (both are isomers) with similar structures, and is easy to cause inaccurate quantification due to peak overlapping, and the gas chromatography-mass spectrometry (GC-MS) method combines the high separation capacity of gas chromatography with the high sensitivity and high selectivity of mass spectrometry, so that impurity characteristic ions can be accurately captured through a Selective Ion Monitoring (SIM) mode, and matrix interference can be effectively eliminated. The Chinese patent publication No. CN112697939A discloses a method for measuring various components in a chest-widening aerosol based on GC-MS/MS, which has advantages in multicomponent synchronous quantification, but faces key technical bottlenecks in practical application and limits the completeness and universality of the method. Firstly, there are significant disadvantages in chromatographic separation, in which the chromatograms of isoborneol and alpha-humulene are completely co-flowed, while the isomers of isoborneol fail to achieve baseline separation, although co-flowed interference can be resolved with high selectivity by GC-MS/MS, for common GC-MS this co-flowed problem can lead to mixed mass spectrograms, making qualitative and quantitative analysis extremely difficult. Secondly, the existing methods are mainly developed for aerosol dosage forms, and the matrix effect of the concentrated solution for injection with complex matrix can interfere the chromatographic behavior of the target compound to correspond to mass spectrum, thus the specificity of the method is a significant challenge. In the prior art, although some methods about drug impurity detection are reported, the specific detection methods for camphor, isoborneol and L-borneol in the concentrate solution for edaravone right camphol injection are less, and some methods have the problems of weak specificity, low sensitivity, poor accuracy and the like, so that strict requirements for drug quality control are difficult to meet. Therefore, the development of the detection method with strong specificity, high sensitivity, good accuracy, good stability and strong durability has important significance for guaranteeing the quality and medication safety of the edaravone dextroamphetamine concentrated solution for injection. Disclosure of Invention The technical problem to be solved by the invention is to provide a GC-MS method for measuring the contents of camphor, isoborneol and L-borneol in the concentrate solution for edaravone right-camphene injection, and the method can be used for rapidly, effectively, accurately and reliably separating and detecting the contents of camphor, isoborneol and L-borneol in the edaravone right-camphene injection, thereby being beneficial to improving the product quality in the edaravone right-camphene injection and improving the medication safety of patients. In order to solve the technical problems, the invention adopts the following technical scheme: The GC-MS method is used for measuring the contents of camphor, isoborneol and L-borneol in the concentrate solution for edaravone right camphol injection, and a gas chromatography-mass spectrometry method is adopted, and the method comprises the following steps: 1) Preparing a sample solution, an impurity stock solution, a reference substance solution and a system applicability solution; 2) Setting