CN111679010A - High performance liquid chromatography detection method for Ruideciclovir intermediate GS-441524 - Google Patents
High performance liquid chromatography detection method for Ruideciclovir intermediate GS-441524 Download PDFInfo
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Abstract
The invention discloses a high performance liquid chromatography detection method of a Rudexilwei intermediate GS-441524, which comprises the following steps: a. preparing a standard solution; b. detecting the standard solution by adopting reverse high performance liquid chromatography; c. the content of GS-441524 in the sample was calculated as peak area by external standard method. The detection method of the invention can ensure that GS-441524, raw materials and other impuritiesThe substances are well separated on a high performance liquid chromatograph; within 1.0-20 mu g/mL, the linear relation is good, R2=0.9997, the average recovery rate is 97.79% -99.90%, and the precision RSD value of 9 parallel tests is 2.65%.
Description
Technical Field
The invention relates to the technical field of analytical chemistry, in particular to a high performance liquid chromatography detection method of a Rudexiliwei intermediate GS-441524.
Background
Reidesciclovir (Remdesivir) is a nucleoside analogue, is a novel experimental broad-spectrum antiviral drug developed by Jilide science, USA, can inhibit RNA-dependent RNA synthetase (RdRp), GS-441524 is an important intermediate for synthesizing Reidesciclovir, CAS has a registration number of 1191237-69-0, a molecular formula of C12H13N5O4, a molecular weight of 291.267, and an English name of: (2R, 3R, 4S, 5R) -2- (4-aminopyraprolo [2, 1-f ] [1, 2, 4] triazin-7-yl) -3, 4-dihydroxy-5- (hydroxymethy) tetrahydrofuran-2-carbonitile, the chemical structure of which is shown in figure 1, and GS-441524 is both a precursor compound and an active metabolite of Reidesvir.
In general, impurity compounds inevitably exist in GS-441524, detection of the impurity compounds has important significance for quality control of GS-441524 and Reidesciclovir, and high performance liquid chromatography can be used for reverse phase and normal phase classification and is determined by the relative polarities of a stationary phase and a mobile phase; wherein the reversed phase high performance liquid chromatography: the stationary phase with relatively weak polarity is adopted, the solvent with stronger polarity is used as the mobile phase, and the stationary phase is commonly used for separating and detecting non-polar and compounds with weak polarity and has wide application; normal phase high performance liquid chromatography: the method adopts a polar stationary phase and takes a solvent with relatively weak polarity as a mobile phase, and is commonly used for separating and detecting compounds with relatively strong polarity.
Whether the derivative is used as an intermediate or a metabolite of Reidexilvir or is directly used as a medicine, the content of GS-441524 needs to be accurately measured in the fields of analytical chemistry and pharmaceutical analysis, and no report related to the content measurement method of GS-441524 is found in domestic and foreign documents at present, so that the research and development of a detection method of the compound shown in the figure 1, which is simple to operate and high in separation degree, is urgently needed.
Disclosure of Invention
The invention aims to provide a high performance liquid chromatography detection method of a Rudexilvir intermediate GS-441524.
The high performance liquid chromatography detection method of the Ruideciclovir intermediate GS-441524 provided by the invention comprises the following steps:
step a, preparing a standard solution: accurately weighing 0.050g of GS-441524 reference substance, dissolving with methanol/water (1: 9, v/v) solution to obtain solution with concentration of 0.2-20 μ g/mL, and filtering with 0.22 μm microporous membrane to obtain standard solution;
and b, detecting the standard solution by adopting a reversed-phase high performance liquid chromatography under the following detection conditions:
stationary phase of chromatographic column: silica gel with nonpolar octadecyl functional group (ODS) bonded on the surface is used as a filler;
mobile phase: methanol and 0.2% aqueous formic acid at a fixed ratio of 1:9 (v/v);
detection wavelength: 230-320 nm;
and c, calculating the content of GS-441524 in the sample by peak area according to an external standard method.
Further, in the step a, the concentration of the standard solution is 0.2-20 mu g/mL.
Furthermore, in the step b, the inner diameter is 2.1mm, the length is 50-150 mm, and the particle size of the filler is 1.7-1.8 μm.
Further, in step b, the chromatographic column is a C18 alkylsilane bonded silica gel packed chromatographic column.
Further, in step b, two mobile phases of methanol and 0.2% aqueous formic acid are used as eluent, and the volume ratio of the two mobile phases is 1: 9.
Further, in the step b, the detector is a diode array or an ultraviolet detector, and the detection wavelength range is 230-320 nm.
Further, in the step b, the column temperature is 35 ℃; the flow rate is 0.2-0.3 mL/min.
Furthermore, in the step b, the sample injection amount is 1-5 mu L.
Further, in the step b, the analysis time is 5-10 min.
Due to the adoption of the technical scheme, the invention has the advantages and positive effects that: the detection method disclosed by the invention can realize complete separation of GS-441524 and impurity compounds without gradient elution, the minimum separation degree is more than 2.0, the number of theoretical plates is high, the influence of interference among components on the accuracy of a detection result is effectively avoided, and meanwhile, the detection method disclosed by the invention has the advantages of simplicity and convenience in operation, accurate and reliable detection result, short analysis time and the like.
Drawings
The invention has the following 7 attached drawings:
FIG. 1 is the chemical structure of GS-441524;
FIG. 2 is the test results of example 1 for detecting the wavelength;
FIG. 3 is a linear relationship diagram of test example 1;
FIG. 4 is the result of measurement of a test sample solution of example 1;
FIG. 5 shows the results of the precision test;
FIG. 6 is the results of a recovery test;
FIG. 7 shows the results of the sample stability test.
Detailed Description
The technical solutions in the embodiments of the present invention are clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, rather than all embodiments, and all other embodiments obtained by a person of ordinary skill in the art without creative efforts based on the embodiments of the present invention belong to the protection scope of the present invention.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways than those specifically described and will be readily apparent to those of ordinary skill in the art without departing from the spirit of the present invention, and therefore the present invention is not limited to the specific embodiments disclosed below.
The GS-441524 control used in the examples was obtained from a commercial product, requiring a purity of greater than 99.0% and no more than 0.5% of other single impurities.
Example 1
1. Instruments and reagents
High performance liquid chromatography (Agilent-1290, USA with DAD detector); analytical balance (sartorius bsa224S, sartorius scientific instruments (beijing) ltd.); an ultrasonic cleaning apparatus (KQ-100DE type, ultrasonic instruments Co., Ltd., Kunshan city); GS-441524 control (commercially available, content > 99%); methanol was chromatographically pure water prepared by a water purifier (Milli-Qdirect 8, Millipore, France) and the other reagents were analytical grade reagents.
2. Content detection of GS-441524 in sample
A. Preparation of test samples
Precisely weighing 50mg of powdery test sample, carrying out ultrasonic dissolution by using about 200mL of methanol/water (1: 9, v/v) solution, fixing the volume to a 250mL volumetric flask to obtain an initial sample solution, diluting the initial sample solution by using 20 times of methanol/water (1: 9, v/v) solution to prepare the test sample solution, and filtering the test sample solution by using a 0.22 mu m microporous filter membrane to be tested.
B. Preparing standard solution
Accurately weighing 50mg of GS-441524 reference substance, ultrasonically dissolving with methanol/water (1: 9, v/v) solution, diluting to 250mL to obtain mother liquor, gradually diluting the mother liquor with methanol/water (1: 9, v/v) solution to obtain 0.2 μ g/mL, 0.5 μ g/mL, 1.0 μ g/mL, 5.0 μ g/mL, 10 μ g/mL, 15 μ g/mL, 20 μ g/mL series standard solutions, filtering with 0.22 μm microporous membrane, and testing.
3. Chromatographic conditions
The chromatographic column was ACQUITYUPLCBEHC18 (2.1X 50mm, 1.7 μm) from Waters (USA); the volume ratio of the mobile phase is methanol to water (0.2% formic acid) =1:9(V/V), and the mobile phase is subjected to ultrasonic degassing treatment for 30 minutes by an ultrasonic instrument before use so as to remove bubbles in the mobile phase; the column temperature was 35 ℃, the detection wavelength of the ultraviolet detector was 240nm, the flow rate was 0.2mL/min, and the sample volume was 2. mu.L.
Determination of detection wavelength test:
and (3) performing full-wavelength spectrum scanning on the sample at 190-400 nm by using an ultraviolet spectrophotometer, and detecting the ultraviolet absorption wavelength of GS-441524, wherein the test result is shown in figure 2.
Test results show that the wavelengths of 240nm and 300nm are strong absorption peaks of GS-441524; under the wavelength of 300nm, the absorption of other impurities is weak, and the impurities cannot be detected completely, and a series of wavelength tests show that the 240nm wavelength is used for detection, so that all the impurities can be scanned; the detection wavelength is in the range of 235 nm-245 nm, and the method is suitable for the high performance liquid chromatography detection method.
Tests were carried out for the selection of the type of mobile phase and the ratio of the two phases; when methanol is used as an organic phase, 0.2% formic acid water is used as an inorganic phase, and the ratio of the organic phase to the inorganic phase is 1:9(V/V), the chromatographic separation process is completed within 8min, in the obtained spectrogram, each peak is symmetrical in shape, the separation degree is high, the Retention Time (RT) of GS-441524 is about 1.46min, and the test result is satisfactory.
4. Linear range investigation
Taking 1.0 mu g/mL, 5.0 mu g/mL, 10 mu g/mL, 15 mu g/mL and 20 mu g/mL series of standard solutions, sequentially analyzing, taking 2 mu L of each standard solution, injecting the standard solution into a liquid chromatograph, measuring according to the method of the invention, recording a chromatogram, drawing a standard curve graph by taking the concentration C (mu g/mL) of the standard solution as an abscissa and taking the peak area A as an ordinate, and calculating through standard curve data to obtain a linear regression equation y =28.619x-3.5235 and a linear correlation coefficient R2=0.9997 as shown in FIG. 3, which indicates that the linear relationship of GS-441524 is good in the range of 1.0 mu g/mL-20 mu g/mL.
5. Detection of GS-441524 content in sample
And (3) injecting 2.0 mu L of the sample solution into a liquid chromatograph, developing according to the method of the invention, recording a chromatogram to obtain a graph 4, repeating for 3 times, substituting the average value of the peak areas of chromatographic peaks corresponding to retention time RT =1.46min in 3 experiments into a linear regression equation, and calculating the content of GS-441524 in the sample.
The result shows that the detection method of the invention can well separate GS-441524, raw materials and other impurities on high performance liquid chromatography, thereby the content detection is accurate and reliable;
6. precision survey
Taking a sample solution to be tested, carrying out continuous sample injection for 9 times according to the sample injection amount of 2 mu L, measuring according to the method of the invention, recording the peak area of the sample, and calculating the average value and the Relative Standard Deviation (RSD), wherein the result is shown in figure 5, which shows that the method for measuring the GS-441524 content has high precision, good reproducibility and small relative standard deviation.
7 recovery Rate survey
The control samples are used for preparing three investigated samples with different concentrations, namely low, medium and high, and the recovery rate, the average recovery rate and the RSD obtained by the measurement result are shown in figure 6 according to the method of the invention and 3 times of measurement in parallel.
8. Stability testing of solutions
And (3) placing the prepared test sample, sampling for 0 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours respectively, carrying out sample injection measurement according to the method, recording a chromatogram, and calculating an RSD value according to the peak area of a GS-441524 substance, wherein the result is shown in figure 7, and according to the RSD value, the solution stability of the test sample solution is good when the test sample solution is placed at room temperature for 24 hours.
9. Determination of detection and quantitation limits
The ratio (signal-to-noise ratio, S/N) of the peak height of the GS-441524 substance to the baseline noise in the chromatogram is greater than 3, and the detection limit of the method is 0.5 mu g/mL through experiments, and the quantification limit of the method is 1.0 mu g/mL through experiments by taking the signal-to-noise ratio (S/N) greater than 10 as the quantification limit standard.
The 4-9 methodological investigation test results show that the method has good specificity, the results show that GS-441524 presents a good linear relation in the range of 1.0-20 mug/mL, the regression equation is y =28.619x-3.5235, the correlation coefficient R =0.9997, the precision, the stability and the recovery are good, the average recovery rate is 97.79-99.90%, the method is simple, the content measurement is accurate and reliable, the test time is short, no interference peak exists, the separation degree, the tailing factor and the symmetric factor all accord with the requirements of Chinese pharmacopoeia, the detection result is good, and the method can be used for the inspection and control of the content item.
Claims (9)
1. A high performance liquid chromatography detection method of a Rudexiluwei intermediate GS-441524 is characterized by comprising the following steps: the method comprises the following steps:
a. preparing a standard solution: accurately weighing a GS-441524 reference substance, dissolving the reference substance by using a methanol/water (1: 9, v/v) solution to prepare a solution with the concentration of 1.0-20 mu g/mL, and filtering the solution by using a 0.22 mu m microporous filter membrane to obtain a standard solution;
b. and (3) detecting the standard solution by adopting a reversed-phase high performance liquid chromatography, wherein the detection conditions are as follows: stationary phase of chromatographic column: silica gel with nonpolar octadecyl functional group (ODS) bonded on the surface is used as a filler; mobile phase: methanol and 0.2% aqueous formic acid; detection wavelength: 230-320 nm;
c. the content of GS-441524 in the sample was calculated as peak area by external standard method.
2. The method according to claim 1, wherein the preparation of a sample is characterized in that: the concentration range of the standard solution is 1.0-20 mu g/mL.
3. The method for measuring a content according to claim 1, wherein the preparation of the standard solution comprises: in the step b, the specification of the chromatographic column is as follows: the inner diameter is 2.1mm, the length is 50-150 mm, and the grain diameter of the filler is 1.7-1.8 μm.
4. The method for measuring a content according to claim 1, wherein the method comprises the steps of: the chromatographic column packing used was silica gel bonded with nonpolar octadecyl functional groups (ODS).
5. The method for measuring a content according to claim 1, wherein the method comprises the steps of: two mobile phases of methanol and 0.2% formic acid aqueous solution are used as eluent, and the volume ratio of the eluent is 1: 9.
6. The method for measuring a content according to claim 1, wherein the method comprises the steps of: the detector is a diode array or an ultraviolet detector, and the detection wavelength range is 230-320 nm.
7. The detection method according to claim 1, characterized in that: in the step b, the column temperature is 35 ℃; the flow rate is 0.2-0.3 mL/min.
8. The detection method according to claim 1, characterized in that: in the step b, the sample injection amount is 1-5 mu L.
9. The detection method according to claim 1, characterized in that: in the step b, the analysis time is 5-10 min.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112730659A (en) * | 2020-12-21 | 2021-04-30 | 江苏正济药业股份有限公司 | Method for detecting related substances of Reidesciclovir intermediate |
| CN113092624A (en) * | 2021-04-07 | 2021-07-09 | 河南泰丰生物科技有限公司 | Ruidexiwei-related substance and content determination method |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111205327A (en) * | 2020-02-17 | 2020-05-29 | 南京法恩化学有限公司 | Preparation method of Reidesciclovir |
-
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111205327A (en) * | 2020-02-17 | 2020-05-29 | 南京法恩化学有限公司 | Preparation method of Reidesciclovir |
Non-Patent Citations (5)
| Title |
|---|
| ANA RANOGAJEC等: "Analysis of nucleosides and monophosphate nucleotides from mushrooms with reversedphase HPLC", 《J. SEP. SCI.》 * |
| BRANDI N. WILLIAMSON等: "Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2", 《NATURE》 * |
| NASER F. AL-TANNAK等: "Remdesivir—Bringing Hope for COVID-19 Treatment", 《SCI. PHARM.》 * |
| 刘淑娟等: "抗新型冠状病毒药物——瑞德西韦", 《临床药物治疗杂志》 * |
| 王媛等: "瑞德西韦(remdesivir) 抗冠状病毒应用前景", 《中国抗生素杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112730659A (en) * | 2020-12-21 | 2021-04-30 | 江苏正济药业股份有限公司 | Method for detecting related substances of Reidesciclovir intermediate |
| CN112730659B (en) * | 2020-12-21 | 2022-05-27 | 江苏正济药业股份有限公司 | Method for detecting related substances of Reidesciclovir intermediate |
| CN113092624A (en) * | 2021-04-07 | 2021-07-09 | 河南泰丰生物科技有限公司 | Ruidexiwei-related substance and content determination method |
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