CN113109465B - Quality detection method and application of entacapone - Google Patents
Quality detection method and application of entacapone Download PDFInfo
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- JRURYQJSLYLRLN-BJMVGYQFSA-N entacapone Chemical compound CCN(CC)C(=O)C(\C#N)=C\C1=CC(O)=C(O)C([N+]([O-])=O)=C1 JRURYQJSLYLRLN-BJMVGYQFSA-N 0.000 title claims abstract description 87
- 229960003337 entacapone Drugs 0.000 title claims abstract description 87
- 238000001514 detection method Methods 0.000 title claims abstract description 43
- 239000012535 impurity Substances 0.000 claims abstract description 62
- 238000000034 method Methods 0.000 claims abstract description 34
- 239000013557 residual solvent Substances 0.000 claims abstract description 17
- 239000000543 intermediate Substances 0.000 claims description 15
- 238000011208 chromatographic data Methods 0.000 claims description 13
- 239000007788 liquid Substances 0.000 claims description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 9
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 9
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 9
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 7
- -1 polysiloxane Polymers 0.000 claims description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- BBFJODMCHICIAA-UHFFFAOYSA-N 3,4-dihydroxy-5-nitrobenzaldehyde Chemical compound OC1=CC(C=O)=CC([N+]([O-])=O)=C1O BBFJODMCHICIAA-UHFFFAOYSA-N 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 4
- 239000000945 filler Substances 0.000 claims description 4
- 230000002194 synthesizing effect Effects 0.000 claims description 4
- INFACQKUQJGVFF-UHFFFAOYSA-N 4-hydroxy-5-methoxy-2-nitrobenzaldehyde Chemical compound COC1=CC(C=O)=C([N+]([O-])=O)C=C1O INFACQKUQJGVFF-UHFFFAOYSA-N 0.000 claims description 3
- 229920000642 polymer Polymers 0.000 claims description 3
- 239000000377 silicon dioxide Substances 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 claims description 3
- 229960000583 acetic acid Drugs 0.000 claims description 2
- 239000012362 glacial acetic acid Substances 0.000 claims description 2
- 229920001296 polysiloxane Polymers 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 claims 1
- 235000012239 silicon dioxide Nutrition 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 239000002904 solvent Substances 0.000 abstract description 4
- 150000001875 compounds Chemical class 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
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- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 4
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 229960004502 levodopa Drugs 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- XDDDOLQEZBJWFZ-LZCJLJQNSA-N (e)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)prop-2-enoic acid Chemical compound OC(=O)C(\C#N)=C\C1=CC(O)=C(O)C([N+]([O-])=O)=C1 XDDDOLQEZBJWFZ-LZCJLJQNSA-N 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 102000006378 Catechol O-methyltransferase Human genes 0.000 description 2
- 108020002739 Catechol O-methyltransferase Proteins 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
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- 229910002027 silica gel Inorganic materials 0.000 description 2
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- 238000012360 testing method Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- PJVWDBNDLNEXCN-FARCUNLSSA-N (e)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-n-methylprop-2-enamide Chemical compound CNC(=O)C(\C#N)=C\C1=CC(O)=C(O)C([N+]([O-])=O)=C1 PJVWDBNDLNEXCN-FARCUNLSSA-N 0.000 description 1
- VDCDWNDTNSWDFJ-UHFFFAOYSA-N 3,5-dinitrocatechol Chemical compound OC1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1O VDCDWNDTNSWDFJ-UHFFFAOYSA-N 0.000 description 1
- 206010030312 On and off phenomenon Diseases 0.000 description 1
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- 230000009286 beneficial effect Effects 0.000 description 1
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- 239000003543 catechol methyltransferase inhibitor Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
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- 238000007865 diluting Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
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- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- OVHHHVAVHBHXAK-UHFFFAOYSA-N n,n-diethylprop-2-enamide Chemical compound CCN(CC)C(=O)C=C OVHHHVAVHBHXAK-UHFFFAOYSA-N 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 238000011112 process operation Methods 0.000 description 1
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- 238000000746 purification Methods 0.000 description 1
- 238000012372 quality testing Methods 0.000 description 1
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- 239000010409 thin film Substances 0.000 description 1
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
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- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
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Abstract
The invention belongs to the field of drug analysis, and discloses a method for detecting the quality of entacapone and application thereof. The quality detection method comprises the steps of comparing a chromatogram of the entacapone to be detected with a standard chromatogram of a residual intermediate, frequently-occurring impurities and a common solvent in the synthesis process of the entacapone, and finally outputting a quality detection result of the entacapone. The method can shorten the quality detection time of the entacapone, can detect and judge various impurities contained in the entacapone at the same time, and prevents the entacapone from deteriorating due to the impurities and residual solvent caused by overlong time for waiting for a detection result. The method is suitable for the quality detection of the pharmaceutical compound, in particular for the quality detection of entacapone.
Description
Technical Field
The invention belongs to the field of drug analysis, and relates to a quality detection method and application of a drug compound, in particular to a quality detection method and application of entacapone.
Background
Entacapone (entacapone) is chemically (E) -2-cyano-3- (3, 4-dihydroxy-5-nitrophenyl) -N, N-diethyl-2-acrylamide and has the formula:
entacapone is a new generation COMT (catechol-O-methyltransferase) inhibitor, is a high-efficiency COMT inhibitor with strong selectivity, small toxicity and activity after oral administration, is used for treating Parkinson's disease, can effectively inhibit O-methylation of levodopa, increase the bioavailability of levodopa in the center, reduce the dosage and the administration frequency of levodopa, and improve the motor fluctuation caused by long-term treatment of levodopa.
For the preparation method and purification process of entacapone, many reports have been made, and the chemical reaction formula is:
however, in the preparation process, in order to shorten the process flow, the intermediate prepared in each step is often simply treated, or even directly subjected to the next reaction without treatment, which results in that the final product entacapone is mixed with the reactants of the previous step, impurities generated by side reactions and residual solvents in each reaction.
At present, aiming at the quality management of entacapone, although the content of impurities in the entacapone is specified to be within a certain range, the detection method is that the entacapone to be detected is detected by using a high performance liquid chromatogram under certain conditions, the retention time of a plurality of larger peaks is selected, the impurities which have the peaks at the retention time are identified one by one, so that the entacapone detection needs to repeat the operation and detection steps to identify the impurities in the entacapone one by one and calculate the content of the impurities in the entacapone, the detection process is tedious and complicated, side reactions are likely to occur in the detection period due to the doped impurities and residual solvents in the entacapone, and the detection result is inaccurate.
Disclosure of Invention
In order to solve the above disadvantages in the prior art, the present invention aims to provide a method for detecting the quality of entacapone and its intermediates, so as to achieve the purposes of shortening the detection time, and rapidly analyzing and confirming the types and contents of various impurities and residual solvents.
In order to realize the purpose, the technical scheme adopted by the invention is as follows:
the method comprises the steps of respectively inputting chromatographic data of an intermediate, common impurities and residual solvents in the process of synthesizing entacapone and chromatographic data of entacapone to be detected, comparing the chromatographic data with the chromatographic data in a comparison module, inputting the compared data into a data output module, and sorting, judging and outputting a quality detection result;
wherein,
the comparison module is used for comparing the chromatographic data of the intermediate, common impurities and residual solvents in the process of synthesizing the entacapone with the chromatographic data of the entacapone to be detected;
the data output module is used for sorting, judging and outputting the quality detection result of the entacapone to be detected;
as a limitation of the present invention, the intermediates include nitrovanillin and 3, 4-dihydroxy-5-nitrobenzaldehyde;
the common impurities include (2Z) -2-cyano-3- (3, 4-dihydroxy-5-nitrophenyl) -N, N-diethyl-2-acrylamide, (2E) -ethyl 2-cyano-3- (3, 4-dihydroxy-5-nitrophenyl) -2-acrylate, 3, 4-dihydroxy-5-nitrobenzaldehyde, (2E) -2-cyano-3- (3-ethoxy-4-hydroxy-5-nitrophenyl) -N, N-diethyl-2-acrylamide, 3, 5-dinitro-1, 2-benzenediol, (2E) -2-cyano-3- (3, 4-dihydroxy-5-nitrophenyl) -2-propenoic acid, (2E) -2-cyano-3- (3, 4-dihydroxy-5-nitrophenyl) -N-methyl-2-propenamide, (2E) -3- (3, 4-dihydroxy-5-nitrophenyl) -2- (piperidine-1-carbonyl) -2-propenoic acid, (2E) -2-cyano-3- (3, 4-dihydroxy-5-nitrophenyl) -2-propenoic acid and (2E) -2-cyano-3- (3, 4-dihydroxy-5-nitrophenyl) -2-propenoic acid N, N-diethyl-2-acrylamide;
the residual solvent comprises methanol, ethanol, isopropanol, tetrahydrofuran, dichloromethane, N-diethyl cyanoacetamide and glacial acetic acid;
as another limitation of the present invention, the separation degree of an impurity peak from an entacapone peak in the chromatographic data of the entacapone is not less than 1.5, and the peak area of the impurity peak in the entacapone to be detected is not less than 0.5 times of the peak area of the corresponding impurity in the impurity control sample;
wherein, the separation degree calculation formula is as follows:
in the formula: t is t R1 Retention time for entacapone;
t R2 retention time for any one impurity;
W 1 the peak width of the chromatographic peak of entacapone;
W 2 is retention time of t R2 Peak width of chromatographic peak;
the invention also provides the application of the quality detection method of the entacapone, which is used for detecting the residual intermediate, impurities and residual solvent in the entacapone.
Due to the adoption of the technical scheme, compared with the prior art, the invention has the following beneficial effects:
(1) According to the method for detecting the quality of the entacapone, the types of impurities contained in the entacapone to be detected and the types and the content of residual solvents can be rapidly screened out;
(2) The method for detecting the quality of entacapone can simultaneously detect various impurities and can also screen the impurities to judge whether new impurities are generated;
(3) The method for detecting the quality of the entacapone can detect the content of residual solvent in a sample to be detected while detecting impurities;
in conclusion, the method for detecting the quality of entacapone provided by the invention can be used for quickly detecting various impurities contained in the entacapone, shortening the detection time, improving the production efficiency and preventing the prepared product from deteriorating due to the impurities and residual solvent.
The method is suitable for the quality detection of the pharmaceutical compound, in particular to the method for detecting the quality of entacapone.
Drawings
The invention is described in further detail below with reference to the following figures and specific examples.
FIG. 1 is a logic diagram of the method for detecting the quality of entacapone provided by the present invention;
FIG. 2 is a high performance liquid chromatogram of a control sample D1 in example 1 of the present invention;
FIG. 3 is a high performance liquid chromatogram of a sample R1 to be measured in example 1 of the present invention;
FIG. 4 is a high performance liquid chromatogram of a control D3 in example 3 of the present invention;
FIG. 5 is a final output interface of an embodiment of the present invention.
Detailed Description
Preferred embodiments of the present invention will be described below with reference to the accompanying drawings. It should be understood that the description of the preferred embodiment is only for purposes of illustration and understanding, and is not intended to limit the invention.
Example 1 method for the quality detection of Entacapone M1
The present example provides a method M1 for the quality detection of entacapone, as shown in fig. 1, comprising the following steps:
s1, respectively weighing common impurities in the synthesis process of 5mg of entacapone, wherein the specific common impurity types are shown in Table 1, uniformly mixing, dissolving with 10ml of acetonitrile, adding 1ml of acetonitrile into a 10ml volumetric flask, adding acetonitrile to a scale mark to fix the volume, adding 1ml of solution from the 10ml volumetric flask into a 100ml volumetric flask, adding acetonitrile to the scale mark to fix the volume, preparing into an impurity solution with the concentration of 0.5%, taking 1ml of the impurity solution, injecting into a high performance liquid chromatograph, and testing by using phenyl bonded silica gel as a filler according to a high performance liquid chromatography (the national pharmacopoeia 2015 edition four-part general regulation 0512); a chromatogram was recorded using a sodium dihydrogenphosphate buffer (2.34 g of sodium dihydrogenphosphate was taken, water was added to 1000ml, pH was adjusted to 2.2 with phosphoric acid) -organic phase (90) as mobile phase a, organic phase-water (80) as mobile phase B, and as shown in fig. 2, this was stored as control sample D1 in the alignment module,
wherein, the organic phase is methanol with a volume ratio of 92: tetrahydrofuran;
table 1: list of common impurities in the synthesis of entacapone
S2, weighing 5mg of entacapone, dissolving the entacapone with 5ml of acetonitrile, adding 1ml of the entacapone into a 10ml volumetric flask, adding the acetonitrile into a scale mark to achieve a constant volume, adding 1ml of solution from the 10ml volumetric flask into a 100ml volumetric flask, adding the acetonitrile into the volumetric flask until the scale mark to achieve the constant volume to prepare a solution with the concentration of 0.1%, taking 1ml of the solution, injecting the solution into a high performance liquid chromatograph, and using phenyl bonded silica gel as a filling agent; performing high performance liquid chromatography (0512 in the fourth part of pharmacopeia 2015 edition of China general rules of general rules) by taking sodium dihydrogen phosphate buffer (2.34 g of sodium dihydrogen phosphate, adding water to 1000ml, and adjusting the pH value to 2.2 by using phosphoric acid) as a mobile phase, recording a chromatogram, and inputting the chromatogram as a sample to be detected R1 into a comparison module as shown in figure 3;
s3, carrying out data analysis processing on the sample R1 to be measured, and calculating a formula according to the separation degree:
in the formula: t is t R1 Retention time for entacapone;
t R2 retention time for any one impurity;
W 1 the peak width of the chromatographic peak of entacapone;
W 2 for retention time of t R2 Peak width of chromatographic peak;
respectively calculating the degrees of separation of each peak and the entacapone from left to right in the graph 3 to be 0.9, 1.06, 1.08, 0.99, 1.52, 1.37, 1.07, 0.8, 1.04 and 1.42 respectively, comparing the residual impurity peaks with a reference sample D1 after the peak with the degree of separation of the peaks with the entacapone being less than 1.5 is removed, marking the corresponding impurity peaks in the sample R1 to be detected according to the peak emergence time of the impurities in the reference sample D1, calculating the ratio of the peak area of the impurity peak corresponding to the reference sample D1, and calculating the calculation result to be 1.8, meanwhile calculating the ratio of the sum of the peak areas of other impurity peaks except the maximum impurity peak in the sample R1 to be detected to the peak area of the entacapone, and finally inputting the comparison result to a data output module together with the previous comparison result;
s4, screening comparison data input by the impurity comparison module respectively, and removing impurities of which the ratio of the peak areas of impurities and solvent peaks contained in the sample R1 to be detected to the peak area of a corresponding impurity peak in the comparison sample D1 is less than 0.5; screening out the peak area of the impurity appearing in the sample R1 to be detected, and respectively outputting the chemical formula of the impurity at the final interface if the ratio of the peak area of the impurity appearing in the sample R1 to the peak area of the impurity appearing in the corresponding peak appearing time in the reference sample D1 is more than 1.5, as shown in figure 5;
and judging that the ratio of the sum of the peak areas of the remaining impurity peaks to the peak area of the entacapone peak is greater than 2 except the maximum impurity peak corresponding to the reference sample D1 in the sample R1 to be detected, and correspondingly outputting a corresponding product to be detected to be unqualified on the final interface, as shown in figure 5.
Example 2 method for the quality detection of Entacapone M2
The method for detecting the quality of entacapone M2 provided in this example 2 is substantially the same as that of example 1, except that the common impurities in the control sample D1 in step S1 are replaced by the residual solvent in the control sample D2. The specific difference steps are that respectively measuring common solvents in the synthesis process of 5mg of entacapone, the specific types are shown in table 2, quantitatively diluting with dimethyl sulfoxide to prepare a mixed solution containing 0.6mg, 1.0mg, 0.14mg, 0.12mg, 1.0mg and 0.5mg in each 1ml, taking a capillary column with (5% phenyl) -methyl polysiloxane as a stationary liquid as a chromatographic column, injecting into a high performance liquid chromatograph by adopting a headspace, keeping the initial temperature at 40 ℃ according to (0861 in the fourth pharmacopoeia of China), keeping the temperature for 2min, and keeping the temperature at 180 ℃ at the rate of 15 ℃ per minute for 8min; the temperature of a sample inlet is 200 ℃; the temperature of the detector is 250 ℃; the flow rate of the chromatographic column is 2ml/min; the split ratio is 10; the balance temperature of the headspace bottle is 80 ℃, and the balance time is 30min. Taking a reference substance and a test solution for headspace sample injection, recording a chromatogram, and taking the chromatogram as a reference sample D2 storage comparison module; the other steps were the same as in example 1.
Table 2: list of solvents commonly used in the synthesis of entacapone
Example 3 method for the quality detection of Entacapone M3
This example 3 provides a method M3 for detecting the quality of entacapone, which is substantially the same as that of example 1, except that the control sample D1 in step S1 is replaced with an intermediate of entacapone of the control sample D3, the common intermediates of which are nitrovanillin (intermediate 1) and 3, 4-dihydroxy-5-nitrobenzaldehyde (intermediate 2), of the formula
Its chromatogram, as shown in FIG. 4;
the specific distinguishing step was to use a capped propyl-2-phenylsilane amorphous organo-silica polymer (5 μm) as a filler (size: length =0.25m, diameter =4.6 mm); the reaction solution was washed with sodium dihydrogen phosphate solution (2.34 g of sodium dihydrogen phosphate, water to 1000ml, PH adjusted to 2.1 with phosphoric acid)) -tetrahydrofuran-methanol (540: 20:440 ) as a mobile phase, tetrahydrofuran-methanol (30): 300nm, flow rate: 1.0ml/min.
Example 4 comparison of Entacapone quality testing methods
Detecting corresponding substances by adopting the same detection conditions as those in the examples 1-3, and detecting and distinguishing impurities and residual solvents in the entacapone and intermediate types contained in the entacapone according to a conventional process;
the conventional detection method for single impurities in entacapone comprises the following steps:
obtaining a chromatogram according to the high performance liquid chromatography (0512 in the fourth part of the general rule of Chinese pharmacopoeia 2015) of the entacapone to be detected → recording the retention time of the entacapone and an impurity peak → performing thin film chromatography, matching liquid phase and nuclear magnetism to determine the molecular formula of the impurity → calculating the content of the impurity → sorting out data to obtain a detection report;
if the entacapone contains more than two impurities, the process operation is repeated for n times according to the type number n of the contained impurities.
The detection cycle of the method for detecting the quality of entacapone provided in example 1 (example 2 and example 3 are only different from the detection cycle in terms of impurity direction and liquid chromatography conditions, and do not affect the detection cycle, so example 1 is representative) of the present invention and the purity change of entacapone after the secondary detection are compared, and the comparative data are shown in table 3.
Table 3: comparison data table of Entacapone quality detection method
n represents the amount of impurities contained in entacapone.
The result shows that when one impurity in Entacapone is detected and judged, the detection and judgment time in the embodiment 1 is shorter than that of the conventional detection method, meanwhile, the embodiment 1 can simultaneously detect and judge a plurality of impurities, and the repeated operation of the process can be effectively avoided; the comparison test result also shows that the accuracy of the detection result of the conventional method is reduced because the detection period of the conventional method is longer, and the purity of the entacapone to be detected is changed after the entacapone is placed for a long time, while the method for detecting the quality of the entacapone, which is disclosed by the embodiment 1 of the invention, can obtain the detection result in a shorter time, so that the purity change amplitude of the entacapone is not large during secondary detection, and the method for detecting the quality of the entacapone, which is provided by the invention, is higher in accuracy.
Although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications may be made to the embodiments described above, or equivalents may be substituted for elements thereof. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (1)
1. A method for detecting the quality of entacapone, which is characterized by comprising the following steps: the quality detection method comprises the steps of respectively inputting chromatographic data of an intermediate, common impurities and residual solvents in the process of synthesizing entacapone and chromatographic data of entacapone to be detected, carrying out data comparison in a comparison module, inputting the compared data into a data output module, sorting and judging the data and outputting a quality detection result;
wherein,
the comparison module is used for comparing the chromatographic data of the intermediate, common impurities and residual solvents in the process of synthesizing the entacapone with the chromatographic data of the entacapone to be detected;
the data output module is used for sorting, judging and outputting the quality detection result of the entacapone to be detected;
the chromatographic conditions under which chromatographic data for the intermediate are obtained are:
using a terminated propyl-2-phenyl silane amorphous organic silicon dioxide polymer as a filling agent; the volume ratio is 540:20:440, taking a sodium dihydrogen phosphate solution-tetrahydrofuran-methanol as a mobile phase, taking tetrahydrofuran-methanol with a volume ratio of 30: 300nm, flow rate: 1.0ml/min;
the size of the end-capped propyl-2-phenylsilane amorphous organic silica polymer is 5 μm;
the sodium dihydrogen phosphate solution is prepared by adding water into 2.34g of sodium dihydrogen phosphate to 1000ml, and adjusting pH to 2.1 with phosphoric acid; the intermediates are nitrovanillin and 3, 4-dihydroxy-5-nitrobenzaldehyde;
the chromatographic conditions under which chromatographic data for the residual solvent are obtained are: injecting 5% phenyl-methyl polysiloxane as fixed liquid into high performance liquid chromatograph by using capillary column as chromatographic column, starting at 40 deg.C for 2min, heating to 180 deg.C at 15 deg.C per minute, and maintaining for 8min; the temperature of a sample inlet is 200 ℃; the temperature of the detector is 250 ℃; the flow rate of the chromatographic column is 2ml/min; the split ratio is 10; the balance temperature of the headspace bottle is 80 ℃, and the balance time is 30min;
the residual solvent comprises methanol, ethanol, isopropanol, tetrahydrofuran, dichloromethane, N-diethyl cyanoacetamide and glacial acetic acid.
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