Determination of memantine hydrochloride tablets using the ACQUITY UPLC /Xevo G2-S QTof system
N-(dimethyl adamantane) glycine (DMAG) content
Wang Zhiying Waters Technology (Shanghai) Co., Ltd.
Foreword:
Memantine hydrochloride is an anti-Alzheimer's drug and is the first N-methyl-D-aspartate (NMDA) antagonist that has a significant effect on Alzheimer's disease. It can improve the memory process. Transmittine is well tolerated. It is the first drug approved by the US Federal Food and Drug Administration (FDA) for the treatment of moderate and severe Alzheimer's disease.
N-(dimethyl adamantane) glycine (DMAG) is one of the known impurities in memantine hydrochloride tablets, and its content is not specified in the National Drug Administration Registration Standard (JX20120025). DMAG itself has no UV absorption. The imported drug registration standard is tested by mass spectrometry with internal standard. The detection time is 30 min. This application should directly use the external standard method for the detection of N-(dimethyl adamantane) glycine.
Xevo G2-S QTof provides the most accurate molecular weight, excellent qualitative properties, and excellent quantitative capabilities. This program uses the quantitative ability of Xevo G2-S QTof to detect the content of N-(dimethyl adamantane) glycine in memantine hydrochloride tablets. The Xevo G2-S QTof is quantified by performing a full scan of the sample and extracting the molecular weight of interest from the obtained data for processing calculation. This quantitative detection method has several advantages. One is that the full scan data can get the most comprehensive information of the sample, let us know more about the sample; the second is more conducive to the development method, it is convenient to see if there is co-interference, To ensure the stability and reliability of the method; the third is to quantitatively detect countless compounds at a time; the fourth is to obtain more information from the existing data if an accident investigation occurs afterwards.
Experimental conditions:
Sample preparation: Take 1 piece of memantine hydrochloride tablets, precisely add methanol-water (50:50) 1mL, vortex 2 times, each time 5 seconds, twice every 1 minute, to ensure that the sample completely disintegrates after 0.22 μm micro The membrane was filtered, and 10 μL of the filtrate was accurately weighed and placed in a 1.5 mL injection bottle. The methanol-water (50:50) 990 μL was precisely added and mixed. Preparation of the control solution: respectively, a mixed solution containing the same concentration of memantine hydrochloride and N-(dimethyl adamantane) glycine reference substance, the diluent is methanol-water (50:50), the concentration of the reference solution of No. 1 to No. 10 , as shown in Table 1.
Results and discussion:
The method of collecting the imported drug registration standard takes a long time, 30 min, and uses a 1.7 μm BEH C18 100 x 2.1 mm column. The HPLC to UPLC method converter converts the method synchronously, and the acquisition time can be shortened. Up to 5 min. And the trifluoroacetic acid in the mobile phase was changed to a solution of formic acid. The separation between DMAG and memantine hydrochloride is good, as shown in Figure 1.
Sensitivity test: the reference product No. 10 solution, that is, the content of DMAG is 1 ng/mL, when entering 3 μL, S/N (PtP) = 41.7; when the injection volume is changed to 1 μL
When S/N(PtP)=10.9, the sample loading on the column is 1 pg, and this concentration can be used as the limit of quantification, as shown in Fig. 2.
Figure 2. Extracted ion chromatogram of DMAG: Control solution No. 10 into 3 μL,
Control solution No. 10 into 1 μL
Reproducibility: Enter the reference solution No. 9 with a DMAG concentration of 10 ng/mL and repeat the injection three times with %RSD=0.47. TargetLynx automatically performs mass extraction, peak area integration and calculation, as shown in Figure 3.
Figure 3. TargetLynx software automatically calculates the %RSD of the DMAG obtained by continuously feeding three doses of the reference solution No. 9.
Linearity: The regression curve is used in the y=ax2+bx+c method of the import registration standard. The results obtained are shown in Figure 4. The application software automatically calculates the linearity, and the obtained linear equation is y=-0.000919094X2 +15.9004X-1.93231; r=0.9994; the TargetLynx interface is simple, and the linear equation information and the content of DMAG in the test sample can be quickly read from the result list. The test product memantine hydrochloride contained 6.1 ng/mL of N-(dimethyl adamantane) glycine.
Figure 4. Automatic linear regression of TargetLynx software to automatically calculate the amount in the sample
in conclusion:
In this experiment, the conventional HPLC column detection method was parallelized into a sub-2 μm UPLC column, and the analysis time was shortened from 30 min to
5 min, greatly improving the efficiency of analysis. On the one hand, Xevo G2-S QTof gives the most accurate molecular weight for the characterization of compounds, and also stands out in terms of quantification. With high sensitivity, N-(dimethyl adamantane) glycine column loading of 1 pg can be quantitatively detected; with good reproducibility, three-needle reproducibility %RSD=0.47% (10 ng/mL) Wide linear range, concentration range of 1~5000 ng/mL, linear equation coefficient R=0.9994. The software MassLynx/TargetLynx is easy to use, automatically performs linear regression and calculates the amount in the sample. Therefore, the ACQUITY UPLC /Xevo G2-S QTof system excels in both qualitative and quantitative aspects, and is fully capable of meeting drug development.
Analyze the process requirements.
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