CN106018604A - Method for measuring dissolution rates of esomeprazole magnesium enteric-coated preparation in different media - Google Patents
Method for measuring dissolution rates of esomeprazole magnesium enteric-coated preparation in different media Download PDFInfo
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- CN106018604A CN106018604A CN201610357133.3A CN201610357133A CN106018604A CN 106018604 A CN106018604 A CN 106018604A CN 201610357133 A CN201610357133 A CN 201610357133A CN 106018604 A CN106018604 A CN 106018604A
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- esomeprazole magnesium
- dissolution
- enteric coated
- coated preparation
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- KWORUUGOSLYAGD-WLHYKHABSA-N magnesium;5-methoxy-2-[(r)-(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]benzimidazol-1-ide Chemical compound [Mg+2].C([S@@](=O)C=1[N-]C2=CC=C(C=C2N=1)OC)C1=NC=C(C)C(OC)=C1C.C([S@@](=O)C=1[N-]C2=CC=C(C=C2N=1)OC)C1=NC=C(C)C(OC)=C1C KWORUUGOSLYAGD-WLHYKHABSA-N 0.000 title claims abstract description 91
- 229960000197 esomeprazole magnesium Drugs 0.000 title claims abstract description 90
- 238000004090 dissolution Methods 0.000 title claims abstract description 57
- 238000002360 preparation method Methods 0.000 title claims abstract description 55
- 238000000034 method Methods 0.000 title claims abstract description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 128
- 239000012535 impurity Substances 0.000 claims abstract description 32
- 239000000706 filtrate Substances 0.000 claims abstract description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 29
- 239000002775 capsule Substances 0.000 claims abstract description 23
- 230000014759 maintenance of location Effects 0.000 claims abstract description 21
- 238000012417 linear regression Methods 0.000 claims abstract description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 238000001914 filtration Methods 0.000 claims abstract description 5
- 239000002662 enteric coated tablet Substances 0.000 claims abstract description 3
- 239000000243 solution Substances 0.000 claims description 115
- 239000013558 reference substance Substances 0.000 claims description 28
- 238000012360 testing method Methods 0.000 claims description 24
- 229910019142 PO4 Inorganic materials 0.000 claims description 20
- 239000010452 phosphate Substances 0.000 claims description 20
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 19
- 238000003556 assay Methods 0.000 claims description 17
- 239000012738 dissolution medium Substances 0.000 claims description 14
- 239000008188 pellet Substances 0.000 claims description 14
- 239000008366 buffered solution Substances 0.000 claims description 13
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- 238000001514 detection method Methods 0.000 claims description 11
- 230000002829 reductive effect Effects 0.000 claims description 11
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 claims description 10
- 229960000381 omeprazole Drugs 0.000 claims description 10
- 239000000843 powder Substances 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 238000010790 dilution Methods 0.000 claims description 5
- 239000012895 dilution Substances 0.000 claims description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 4
- -1 hydrogen Sodium hydroxide Chemical class 0.000 claims description 4
- 239000011777 magnesium Substances 0.000 claims description 4
- 229910052749 magnesium Inorganic materials 0.000 claims description 4
- 238000005070 sampling Methods 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- FGDQGIKMWOAFIK-UHFFFAOYSA-N acetonitrile;phosphoric acid Chemical compound CC#N.OP(O)(O)=O FGDQGIKMWOAFIK-UHFFFAOYSA-N 0.000 claims description 3
- 229960004770 esomeprazole Drugs 0.000 claims description 3
- SUBDBMMJDZJVOS-DEOSSOPVSA-N esomeprazole Chemical compound C([S@](=O)C1=NC2=CC=C(C=C2N1)OC)C1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-DEOSSOPVSA-N 0.000 claims description 3
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 3
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 3
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 2
- 235000019800 disodium phosphate Nutrition 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims description 2
- 239000012530 fluid Substances 0.000 claims description 2
- 239000001488 sodium phosphate Substances 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 2
- 239000011734 sodium Substances 0.000 claims 2
- 229910052708 sodium Inorganic materials 0.000 claims 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 1
- 150000002825 nitriles Chemical class 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000007788 liquid Substances 0.000 abstract description 18
- 230000008901 benefit Effects 0.000 abstract description 3
- 238000004364 calculation method Methods 0.000 abstract description 3
- 230000008859 change Effects 0.000 abstract description 3
- 235000019441 ethanol Nutrition 0.000 abstract 1
- 230000035945 sensitivity Effects 0.000 abstract 1
- 239000003826 tablet Substances 0.000 description 20
- 239000002609 medium Substances 0.000 description 17
- 239000012736 aqueous medium Substances 0.000 description 13
- 239000008363 phosphate buffer Substances 0.000 description 11
- 239000002253 acid Substances 0.000 description 9
- 230000015556 catabolic process Effects 0.000 description 9
- 238000006731 degradation reaction Methods 0.000 description 9
- 230000008569 process Effects 0.000 description 7
- 238000002386 leaching Methods 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 230000004044 response Effects 0.000 description 4
- 238000010812 external standard method Methods 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000000205 computational method Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000004570 mortar (masonry) Substances 0.000 description 2
- 210000001711 oxyntic cell Anatomy 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000003672 processing method Methods 0.000 description 2
- JGSARLDLIJGVTE-UHFFFAOYSA-N 3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-UHFFFAOYSA-N 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 230000027119 gastric acid secretion Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- KWORUUGOSLYAGD-UHFFFAOYSA-N magnesium 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methylsulfinyl]benzimidazol-1-ide Chemical compound [Mg+2].N=1C2=CC(OC)=CC=C2[N-]C=1S(=O)CC1=NC=C(C)C(OC)=C1C.N=1C2=CC(OC)=CC=C2[N-]C=1S(=O)CC1=NC=C(C)C(OC)=C1C KWORUUGOSLYAGD-UHFFFAOYSA-N 0.000 description 1
- MQEUGMWHWPYFDD-UHFFFAOYSA-N magnesium;6-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound [Mg].N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C MQEUGMWHWPYFDD-UHFFFAOYSA-N 0.000 description 1
- YYINWHOQKIUBNL-UHFFFAOYSA-N magnesium;trihydrate Chemical compound O.O.O.[Mg] YYINWHOQKIUBNL-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000003375 sulfoxide group Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
Classifications
-
- 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
-
- 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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- 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
- G01N2030/022—Column chromatography characterised by the kind of separation mechanism
- G01N2030/027—Liquid chromatography
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for measuring the dissolution rates of an esomeprazole magnesium enteric-coated preparation in different media. The method is characterized in that a step of establishing a linear regression equation is added, that is, a sodium hydroxide solution and ethyl alcohol are added into the content of an esomeprazole magnesium enteric-coated tablet or capsule to perform ultrasonic dissolution, then filtration is conducted, the filtrate is taken out, subjected to constant-volume treatment and then placed in a water bath of 37+/-0.5 DEG C, a sample is taken at each dissolution time and is injected into a high performance liquid chromatograph, chromatograms are recorded, and the linear relationship between a main peak and a relative retention time 2.7 impurity peak is found out from the area change relationship between the main peak and the relative retention time 2.7 impurity peak to obtain the linear regression equation which is applied to calculation of the dissolution quantity of esomeprazole magnesium. The method solves the problem that the dissolution rate of the esomeprazole magnesium enteric-coated preparation cannot be accurately measured in the prior art, and has the advantages of being convenient, quick, accurate, excellent in repeatability, high in sensitivity and strong in practicability during operation.
Description
Technical field
The present invention relates to System In Pharmaceutical Preparation Analysis detection field, particularly relate to a kind of esomeprazole magnesium enteric coated preparation and exist
The assay method of dissolution in different medium.
Background technology
Esomeprazole magnesium (Esomeprazole Magnesium, double-S-5-methoxyl group-2-{ [(4-methoxyl group-3,
5-dimethyl-2-pyridine radicals) methyl] sulfenyl-1H-benzimidazole magnesium trihydrate) a kind of new proton pump inhibitor, its
Molecular formula is C34H36MgN6O6S2·3H2O, molecular weight 767.17, chemical structural formula is as follows:
Esomeprazole magnesium, also referred to as esomeprazole magnesium, be the S-configuration optical isomer of omeprazole, and it is weak
Alkalescence, concentration be converted into active matter sulfenic acids amide in parietal cell secretes the high acid environment of sour micro-pipe is then thin with coat of the stomach
H on born of the same parents+-K+Sulfydryl on-ATP enzyme subunit cysteine residues passes through disulfide-bonded, makes the oxidized inactivation of enzyme, thus
Make the H of parietal cell+Gastral cavity can not be transported to, and then play gastric acid secretion inhibiting, and then play the therapeutical effect of gastric acid inhibitory.
There is sulfoxide group in esomeprazole magnesium structure so that it is extremely sensitive to acid medium, easily degrade, this also leads
Cause its process in leaching in the media such as pH6.0 phosphate buffer, pH6.8 phosphate buffer, water is degraded, unfavorable
Accurate calculating in dissolution result.But, retrieve the documents and materials about esomeprazole magnesium preparation dissolution control method
And patent, and find no the research report of related fields.This is the most just difficult to evaluate esomeprazole magnesium enteric system accurately
The process in leaching of agent.
Summary of the invention
Based on this, it is an object of the invention to provide the assay method of a kind of esomeprazole magnesium enteric coated preparation dissolution.
The concrete technical scheme realizing foregoing invention purpose is as follows:
The assay method of a kind of esomeprazole magnesium enteric coated preparation dissolution, comprises the following steps:
(1) preparation of need testing solution a
Take esomeprazole magnesium enteric coated preparation add dissolution instrument dissolution medium in, speed of agitator be 50rpm～
100rpm, temperature is 37 DEG C ± 0.5 DEG C, takes dissolution fluid in different time points and filters, and takes filtrate and adds sodium hydroxide solution, described
The concentration of sodium hydroxide solution is 0.1mol/L～0.5mol/L, and taken filtrate is 1:0.1-with the volume ratio of sodium hydroxide solution
0.14, shake up, be the need testing solution a of each time point；
(2) preparation of esomeprazole magnesium solution b
Take esomeprazole magnesium enteric coated preparation, finely ground, weigh finely ground powder and add sodium hydroxide solution, ultrasonic, add second
Alcohol, continues ultrasonic, quantitatively dilutes with sodium hydroxide solution, obtains solution I, filters, obtains filtrate I, take filtrate I quantitative with described acid medium
Dilution, obtains solution II；Solution II is placed in 37 DEG C ± 0.5 DEG C water-bath, respectively at different time points sampling filtering, obtains each time point
Filtrate II, takes filtrate II and adds sodium hydroxide solution, and taken filtrate II is 1:0.1-0.14 with the volume ratio of sodium hydroxide solution, shakes up,
It is the esomeprazole magnesium solution b of described each time point；The concentration of described sodium hydroxide solution is 0.01mol/L～1.0mol/L；
(3) preparation of reference substance solution
Take omeprazole reference substance, dissolve with ethanol, more quantitatively dilute with dissolution medium, pipette the solution after dilution, add
Enter sodium hydroxide solution, shake up, be reference substance solution；The concentration of described sodium hydroxide solution is 0.1mol/L～0.5mol/
L, the solution after described dilution is 1:0.1-0.14 with the volume ratio of sodium hydroxide solution；
(4) high performance liquid chromatography detection
Step I: carry out need testing solution a and reference substance solution by high performance liquid chromatography, records need testing solution a
Main peak peak area AA masterPeak area A with the impurity peaks that relative retention time is 2.7A is miscellaneous；And the peak area of reference substance solution；
Step II: detect the esomeprazole magnesium solution b of each time point by high performance liquid chromatography, record is each
Time point main peak peak area AB masterPeak area A with the impurity peaks that relative retention time is 2.7B is miscellaneous；Set up each time point relatively to retain
Time is the impurity peaks peak area A of 2.7B is miscellaneousValue added and main peak peak area AB masterReduced value between equation of linear regression y=
Kx+m and its correlation coefficient r, wherein y is the reduced value of main peak peak area, and x is the value added of impurity peaks peak area；
According to the peak area A of the impurity peaks that relative retention time is 2.7 of record in step IA is miscellaneousAnd step II is linear
Regression equation y=kx+m, is calculated the reduced value of the main peak peak area of need testing solution a, adds the master of record in step I
Peak-to-peak area AA master, it is calculated the stripping quantity that esomeprazole magnesium is actual, and then obtains dissolution.
Wherein in some embodiments, described esomeprazole magnesium enteric coated preparation is esomeprazole magnesium enteric coated micropill
Capsule or esomeprazole magnesium enteric coated tablet.
Wherein in some embodiments, described dissolution medium is phosphate buffered solution or the water of pH5.5-7.0.
Wherein in some embodiments, the chromatograph of the high performance liquid chromatography detection described in step (3) and step (4.2)
Condition is:
Chromatographic column: C18 chromatographic column, specification is 5 μm, 4.6*150mm；Flowing phase: acetonitrile-phosphate buffered solution-water, institute
Stating acetonitrile, phosphate buffered solution is 33-37:48-52:13-17 with the volume ratio of water, and the pH of described phosphate buffered solution is
7.2-7.4；Flow velocity: 0.7～0.9mL/min；Sample size: 20 μ L；Column temperature: 25 DEG C～35 DEG C；Detection wavelength: 302nm.
Wherein in some embodiments, described acetonitrile, phosphate buffered solution are 35:50:15 with the volume ratio of water, described
The pH of phosphate buffered solution is 7.3, and its compound method is for taking 1mol/L sodium dihydrogen phosphate 10.5ml and 0.5mol/L phosphorus
Acid disodium hydrogen solution 60ml, is diluted with water to 1000ml, shakes up and get final product；Flow velocity: 0.8mL/min；Column temperature: 30 DEG C.
Wherein in some embodiments, the esomeprazole magnesium in esomeprazole magnesium enteric coated preparation in step (1)
It is 20mg:900-1000mL with the proportioning of dissolution medium；The concentration of described sodium hydroxide solution is 0.25mol/L～0.5mol/
L, taken filtrate is 1:0.12 with the volume ratio of sodium hydroxide solution.
Wherein in some embodiments, the rotating speed of step (1) described stirring is 50rpm～75rpm.
Wherein in some embodiments, ethanol described in step (2) is joined with esomeprazole magnesium enteric coated preparation powder
Ratio is 7～8ml:100mg, the magnesium enteric coated preparation powder 5mg/mL Han esomeprazole in described solution I；Taken filtrate I and institute
The volume ratio obtaining solution II is 1:50.
Wherein in some embodiments, the concentration of sodium hydroxide solution described in step (2) be 0.25mol/L～
0.5mol/L, taken filtrate II is 1:0.12 with the volume ratio of sodium hydroxide solution.
Wherein in some embodiments, in step (3) described reference substance solution, the content of omeprazole is 20 μ g/ml.
Wherein in some embodiments, in step (4) described equation of linear regression y=kx+m, 1.0≤k≤5.0,20000
≤ m≤100000, correlation coefficient r is more than 0.995.
The assay method of the esomeprazole magnesium enteric coated preparation dissolution of the present invention has the following advantages and beneficial effect:
Esomeprazole magnesium enteric coated preparation is degradable in the process in leaching in acid medium, with existing method measure its
During stripping quantity in acid medium, main peak area elapses in time and is gradually reduced, and all peaks of chromatogram on each time point
Peak area summation inconsistent, this causes the stripping quantity that cannot accurately calculate esomeprazole magnesium.The present inventor passes through
Lot of experiments finds, is dissolved in acid medium by esomeprazole magnesium, along with the change of standing time, main peak peak area
The increase of peak area of the impurity peaks that minimizing and relative retention time are 2.7 there is certain linear relationship, therefore inventor's wound
The property made in the test process of its dissolution, add step and the concrete grammar thereof setting up equation of linear regression, i.e. set up main peak
Equation of linear regression between the increase of the peak area of the minimizing of peak area and impurity peaks that relative retention time is 2.7, utilizing should
Regression equation can accurately calculate the time dependent minimizing of main peak area in process in leaching of esomeprazole magnesium enteric coated preparation,
Main peak area further according to practical measurement can accurately calculate esomeprazole magnesium enteric coated preparation difference in acid medium
The dissolution of time point, and then set up stripping curve, this stripping curve can be used to accurate evaluation esomeprazole magnesium enteric
The process in leaching in different medium of preparation, the especially process in leaching in the phosphate buffered solution that pH is 6.0 or water.
Therefore, the assay method of the esomeprazole magnesium enteric coated preparation dissolution of the present invention solve prior art can not
Accurate Determining esomeprazole magnesium enteric coated preparation problem of dissolution in acid medium, the method for the present invention has conveniently,
Fast, accurately, favorable reproducibility, highly sensitive, the advantage such as the most practical.
Accompanying drawing explanation
Fig. 1 is the height that in embodiment 1, esomeprazole magnesium enteric coatel tablets are degraded in the phosphate-buffered liquid medium of pH6.0
Effect liquid phase chromatogram figure；
Fig. 2 is the high-efficient liquid phase chromatogram degraded in esomeprazole magnesium enteric coatel tablets aqueous medium in embodiment 2；
Fig. 3 is esomeprazole magnesium enteric coated preparation dissolution in the phosphate-buffered liquid medium of pH6.0 in embodiment 4
Curve chart；
Fig. 4 is esomeprazole magnesium enteric coated preparation stripping curve figure in aqueous medium in embodiment 5.
Detailed description of the invention
Below in conjunction with specific embodiment, the assay method of the esomeprazole magnesium enteric coated preparation dissolution of the present invention is made
Further describe, but protection scope of the present invention is not limited to these implements row.Every change without departing substantially from present inventive concept
Or within equivalent replacement is included in protection scope of the present invention.
Unless otherwise indicated, raw material or reagent used in following example are commercially available.
In following example, the chromatographic condition of high performance liquid chromatography detection is:
Chromatographic column: C18 post, specification is 5 μm, 4.6*150mm；Flowing phase: acetonitrile-phosphate buffered solution-water, acetonitrile,
The volume ratio of phosphate buffered solution and water is 35:50:15, and the pH of phosphate buffered solution is 7.3 (to join by the following method
System: take 1mol/L sodium dihydrogen phosphate 10.5ml and 0.5mol/L disodium phosphate soln 60ml, be diluted with water to 1000ml,
Shake up)；Flow velocity: 0.8ml/min；Sample size: 20 μ L；Column temperature: 30 DEG C；Detection wavelength: 302nm.
Embodiment 1 esomeprazole magnesium enteric coatel tablets or enteric-coated pellet capsule degradation rule in pH6.0 phosphate buffer
Take specification 20mgEsomeprazole magnesium enteric coatel tablets or enteric-coated pellet capsule (remove capsule shells, in taking
Tolerant, lower with) put in mortar, finely ground, weigh 100mg in 20ml volumetric flask, add 0.0125mol/L sodium hydroxide solution
12mL, ultrasonic 5min, add 7.5ml ethanol and continue ultrasonic 3min, with 0.0125mol/L sodium hydroxide solution constant volume.Filter, take filter
In liquid 2ml to 100ml volumetric flask, with pH6.0 phosphate buffer constant volume, put in 37 DEG C ± 0.5 DEG C water-bath, respectively at 0,15,
30,45,60,90,120,180,240min sampling, filter.Take subsequent filtrate 5ml in cillin bottle, be separately added into 0.5mol/L hydrogen
Sodium oxide 600 μ l, mixing, the accurate 20 μ l that draw inject chromatograph of liquid, record chromatogram.Owing to sample is at pH6.0 phosphate
Buffer is degraded, adds up with the degradation impurity peak of main peak and one of them relative retention time 2.7, the results are shown in Table 1, table
2；And respectively with main peak peak area AMainReduced value as y value, the value added of the impurity peaks peak area of relative retention time 2.7 is made
For x value；AMainMain peak peak area A when reduced value computational methods are main peak 0minMainThis main peak peak being individually subtracted each time point
Area, correspondingly, AMiscellaneousValue added computational methods are the impurity peaks peak area (A at each time point of relative retention time 2.7Miscellaneous)
Deduct this impurity peak area during 0min, carry out regression equation calculation, the results are shown in Table 3 and table 4.
Table 1. esomeprazole magnesium enteric coatel tablets degradation data in the phosphate-buffered liquid medium of pH6.0
Table 2. esomeprazole magnesium enteric-coated pellet capsule degradation data in the phosphate buffer of pH6.0
Table 3. esomeprazole magnesium enteric coatel tablets equation of linear regression in the phosphate buffer of pH6.0
| Sheet number | Regression equation | Correlation coefficient r |
| 1 | Y=3.5587x+42043 | 0.9995 |
| 2 | Y=3.5285x+38124 | 0.9995 |
| 3 | Y=3.5688x+47602 | 0.9995 |
| Averagely | Y=3.5527x+42534 | 0.9997 |
Table 4. esomeprazole magnesium enteric-coated pellet capsule equation of linear regression in the phosphate buffer of pH6.0
| Capsule number | Regression equation | Correlation coefficient r |
| 1 | Y=3.9230x+48002 | 0.9965 |
| 2 | Y=3.4722x+57510 | 0.9950 |
| 3 | Y=3.5605x+59336 | 0.9952 |
| Averagely | Y=3.6563x+54476 | 0.9970 |
Embodiment 2. esomeprazole magnesium enteric coatel tablets or enteric-coated pellet capsule degradation rule in water
Take specification 20mgEsomeprazole magnesium enteric coatel tablets or enteric-coated pellet capsule (remove capsule shells, in taking
Tolerant) put in mortar, finely ground, weigh 100mg in 20ml volumetric flask, with 0.0125mol/L sodium hydroxide solution 12mL, ultrasonic
5min, adds 7.5ml ethanol and continues ultrasonic 3min, 0.0125mol/L sodium hydroxide solution constant volume, filter, take subsequent filtrate 2ml and arrive
In 100ml volumetric flask, adjust pH to 7.0 ± 0.05 with the hydrochloric acid of 0.1mol/L, then use water constant volume, be placed in 37 DEG C ± 0.5 DEG C water-bath
In, respectively at 0,30,60,90,120,180,240,300,360min sampling filtering, take subsequent filtrate 5ml, add 0.25mol/ respectively
L sodium hydroxide 600 μ l, mixing, the accurate 20 μ l that draw inject chromatograph of liquid, record chromatogram.Owing to sample is in aqueous medium
Degraded, adds up with the degradation impurity peak of main peak and a relative retention time 2.7, the results are shown in Table 5 and table 6；With reference to implementing
The data processing method of example 1 is respectively using the reduced value of main peak peak area as y value, the value added conduct of corresponding impurity peaks peak area
X value, carries out regression equation calculation, the results are shown in Table 7 and table 8.
Table 5. esomeprazole magnesium enteric coatel tablets degradation data in aqueous medium
Table 6. esomeprazole magnesium enteric-coated pellet capsule degradation data in aqueous medium
Table 7. esomeprazole magnesium enteric coatel tablets equation of linear regression in aqueous medium
| Sheet number | Regression equation | Correlation coefficient r |
| 1 | Y=4.2901x+66207 | 0.9992 |
| 2 | Y=4.3704x+65325 | 0.9982 |
| 3 | Y=4.848x+83248 | 0.9959 |
| Averagely | Y=4.481x+70939 | 0.9984 |
Table 8. esomeprazole magnesium enteric-coated pellet capsule equation of linear regression in aqueous medium
| Capsule number | Regression equation | Correlation coefficient r |
| 1 | Y=4.4894x+47670 | 0.9984 |
| 2 | Y=4.4383x+46822 | 0.9986 |
| 3 | Y=4.2855x+59080 | 0.9978 |
| Averagely | Y=4.4111x+52818 | 0.9993 |
Embodiment 3. esomeprazole magnesium enteric coatel tablets stripping quantity measures the accuracy (average recovery) of analysis method and tests
Card
(1) average recovery in the phosphate-buffered liquid medium of pH6.0
Prepared by reference substance solution: weigh omeprazole about 20mg, puts in 100ml measuring bottle, dissolves with ethanol and is diluted to carve
Degree, as reference substance solution.
The preparation of need testing solution: take the blank auxiliary in the esomeprazole magnesium enteric coatel tablets prescription of specification 20mg, grind
Carefully, weigh 100mg powder in 100ml volumetric flask, add 0.0125mol/L sodium hydroxide solution, ultrasonic 5min, add ethanol
37.5ml, ultrasonic 3min, it is settled to scale with 0.0125mol/L sodium hydroxide solution.Filter, take subsequent filtrate 5ml and put 100ml appearance
In measuring bottle, take 9 parts altogether, be separately added into reference substance solution 1ml, 3ml, 5ml each three parts in respective volume bottle, use pH6.0 respectively
Phosphate buffer be diluted to scale, shake up, filter, take subsequent filtrate 5ml, add 0.5mol/L sodium hydroxide solution 600ul,
As need testing solution.
The accurate each 20ul of above-mentioned solution of absorption injects chromatograph of liquid, records chromatogram.Relatively protect according to chromatogram record
Stay the peak area of time 2.7 impurity peaks.This impurity peaks peak area of integral and calculating (peak area initial value is 0), substitutes into linear regression
In equation y=3.5527x+42534, calculate the reduced value of main peak peak area, and combine the corresponding main peak of this chromatogram record
Peak area, draws the main peak peak area of reality, calculates the amount of actual esomeprazole magnesium with one point external standard method, utilizes and reclaims
Rate (%)=principal agent measured amount/principal agent addition is multiplied by 100%, calculates the response rate, the results are shown in Table 9.
Table 9. esomeprazole magnesium enteric coatel tablets average recovery in the phosphate-buffered liquid medium of pH6.0
Draw from table 9: the value added of the impurity peaks peak area of relative retention time 2.7 is substituted into this linear regression y=
Trying to achieve the peak area of principal agent degraded, and then the method obtaining total main peak area in 3.5527x+42534, its response rate is good.
Illustrate that the method is accurately and reliably.
(2) average recovery in aqueous medium
Prepared by reference substance solution: weigh omeprazole about 20mg, puts in 50ml measuring bottle, dissolves with ethanol and is diluted to carve
Degree, as reference substance solution.
The preparation of need testing solution: take the blank auxiliary in specification 20mg esomeprazole magnesium enteric coatel tablets prescription and be placed in and grind
In alms bowl, finely ground, weigh 100mg powder in 100ml volumetric flask, add 0.0125mol/L sodium hydroxide solution, ultrasonic 5min,
Add ethanol 37.5ml, ultrasonic 3min, be settled to scale with 0.0125mol/L sodium hydroxide solution.3500rpm is centrifuged 20min,
Take supernatant liquid filtering, take subsequent filtrate 1ml and put in 100ml measuring bottle, take 9 parts altogether, be separately added into reference substance solution 1ml, 3ml, 5ml each
Put in corresponding measuring bottle, be diluted to scale with aqueous medium, shake up for three parts, filter, take subsequent filtrate 5ml, add 0.25mol/L hydroxide
Sodium solution 600ul, as need testing solution.
The accurate each 20ul of above-mentioned solution of absorption injects chromatograph of liquid, records chromatogram.Relatively protect according to chromatogram record
Stay the peak area of time 2.7 impurity peaks.Calculate the value added of this impurity peaks peak area, substitute into equation of linear regression y=4.481x+
In 70939, use the data processing method of embodiment 3. (1), calculate the reduced value of main peak peak area, and plus this chromatograph seal
The corresponding main peak peak area of record, draws the main peak peak area of reality, thus calculates the amount of the esomeprazole magnesium of reality, meter
Calculate the response rate, the results are shown in Table 10.
Table 10. esomeprazole magnesium enteric coatel tablets average recovery in aqueous medium
Draw from table 10, the value added of the impurity peak area of relative retention time 2.7 is substituted into this linear regression y=
4.4111x+52818 asks the peak area obtaining degraded principal agent degraded, and then the method obtaining total main peak area, its response rate
Well.Illustrate that the method is accurately and reliably.
Embodiment 4. esomeprazole magnesium enteric coatel tablets and pellet capsule dissolution in the phosphate-buffered liquid medium of pH6.0
The mensuration of curve
(1) preparation of need testing solution
Take specification 20mg esomeprazole magnesium enteric coatel tablets 6 or esomeprazole magnesium enteric coated micropill enteric coated capsule 6,
Use paddle method dissolution instrument, with reference to Chinese Pharmacopoeia version dissolutions in 2015 and drug release determination method (general rule 0,931 second method method
1), every or every with 1000ml pH 6.0 phosphate buffer as dissolution medium, rotating speed 50rpm, respectively at 15,30,45,
60,90,120, the time of 180min take solution, filter, take subsequent filtrate 5ml and add 0.25mol/L sodium hydroxide solution 600 μ l,
Shake up, as need testing solution.
(2) preparation of reference substance solution
Take omeprazole reference substance 20mg, accurately weighed, put in 100ml measuring bottle, add ethanol 10ml and make dissolving, be situated between with dissolution
Matter is diluted to scale, shakes up, and precision measures in right amount, quantitatively dilutes make in every 1ml containing about 0.02mg molten with this dissolution medium
Liquid, then precision measures 5ml, precision adds 0.25mol/L sodium hydroxide solution 600 μ l, shakes up, as reference substance solution.
(3) high performance liquid chromatography detection
By high performance liquid chromatography, need testing solution and the reference substance solution of the dissolution of each time point are detected,
Chromatogram, record main peak peak area and relative retention time are the peak area of the impurity peaks of 2.7.
The peak area of the impurity peaks of each time point relative retention time 2.7 according to liquid chromatogram record, when calculating each
Between put the value added of this impurity peaks peak area, this value added is substituted into gained equation of linear regression y=3.5527x+42534 (sheet)
Or in y=3.6563x+54476 (pellet capsule), calculate the reduced value of each time point main peak peak area, and plus this chromatograph
Main peak peak area corresponding in figure, draws the main peak peak area that each time point is actual, when calculating each dissolution with one point external standard method
Between put the stripping quantity of reality, calculate dissolution (representing with meansigma methods ± SD), and draw stripping curve, esomeprazole magnesium intestinal
Molten and capsule stripping curve figure in the phosphate-buffered liquid medium of pH6.0 are shown in that Fig. 3, dissolution results are shown in Table 11.Dissolution
Degree computing formula is as follows.
Dissolution computing formula:
Note: ASupply: esomeprazole peak area and degradation peak's area sum thereof in need testing solution
ARight: omeprazole peak area in reference substance solution
CRight: reference substance solution concentration (mg/ml)
PSupply: need testing solution extension rate
Accumulation dissolution computing formula:
Note: An: record dissolution for each time point
V1: each time point fixes sample volume (10ml)
V2: dissolution medium volume, 1000ml
Table 11. esomeprazole magnesium enteric coated preparation dissolution (n=6) in pH6.0 phosphate buffer
Embodiment 5. esomeprazole magnesium enteric coatel tablets and pellet capsule mensuration of stripping curve in aqueous medium
(1) preparation of need testing solution
Take esomeprazole magnesium enteric coatel tablets 6 or the esomeprazole magnesium enteric-coated pellet capsule 6 of specification 20mg, adopt
With paddle method dissolution instrument, with reference to Chinese Pharmacopoeia version dissolutions in 2015 and drug release determination method (general rule 0,931 second method method 1),
Every or every with 1000ml water as dissolution medium, rotating speed is 50rpm, respectively at 30,60,90,120,180,240,300,
The dissolution time point of 360min takes solution, filters, and takes subsequent filtrate 5ml and adds 0.25mol/L sodium hydroxide solution 600 μ l, shakes up,
As need testing solution.
(2) preparation of reference substance solution
Take omeprazole reference substance 20mg, accurately weighed, put in 100ml measuring bottle, add ethanol 10ml and make dissolving, be situated between with dissolution
Matter is diluted to scale, shakes up, and precision measures in right amount, quantitatively dilutes make in every 1ml containing about 0.02mg molten with this dissolution medium
Liquid, then precision measures 5ml, precision adds 0.25mol/L sodium hydroxide solution 600 μ l, shakes up, as reference substance solution.
(3) high performance liquid chromatography detection
By high performance liquid chromatography, need testing solution and the reference substance solution of the dissolution of each time point are detected,
Chromatogram, record main peak peak area and relative retention time are the peak area of the impurity peaks of 2.7.
The peak area of the impurity peaks of each time point relative retention time 2.7 according to liquid chromatogram record, when calculating each
Between put the value added of this impurity peaks peak area, this value added is substituted into gained equation of linear regression y=4.481x+70939 (sheet)
Or in y=4.4111x+52818 (pellet capsule), calculate the reduced value of each time point main peak peak area, and plus this chromatograph
Main peak peak area corresponding in figure, draws the main peak peak area that each time point is total, calculates each dissolution time with one point external standard method
The stripping quantity that point is actual, calculates dissolution (representing with meansigma methods ± SD), and draws stripping curve (with reference to embodiment 4).Ai Si
Magnesium omeprazole enteric coatel tablets and the capsule stripping curve figure in aqueous medium is shown in that Fig. 4, dissolution results are shown in Table 12.
Table 12. esomeprazole magnesium enteric coated preparation dissolution (n=6) in aqueous medium
Each technical characteristic of embodiment described above can combine arbitrarily, for making description succinct, not to above-mentioned reality
The all possible combination of each technical characteristic executed in example is all described, but, as long as the combination of these technical characteristics is not deposited
In contradiction, all it is considered to be the scope that this specification is recorded.
Embodiment described above only have expressed the several embodiments of the present invention, and it describes more concrete and detailed, but also
Can not therefore be construed as limiting the scope of the patent.It should be pointed out that, come for those of ordinary skill in the art
Saying, without departing from the inventive concept of the premise, it is also possible to make some deformation and improvement, these broadly fall into the protection of the present invention
Scope.Therefore, the protection domain of patent of the present invention should be as the criterion with claims.
Claims (10)
1. the assay method of an esomeprazole magnesium enteric coated preparation dissolution, it is characterised in that comprise the following steps:
(1) preparation of need testing solution a
Taking in the dissolution medium that esomeprazole magnesium enteric coated preparation adds dissolution instrument, speed of agitator is 50rpm～100rpm,
Temperature is 37 DEG C ± 0.5 DEG C, takes dissolution fluid in different time points respectively and filters, and takes filtrate and adds sodium hydroxide solution, described hydrogen
The concentration of sodium hydroxide solution is 0.1mol/L～0.5mol/L, and taken filtrate is 1:0.1-with the volume ratio of sodium hydroxide solution
0.14, shake up, be the need testing solution a of each time point；
(2) preparation of esomeprazole magnesium solution b
Take esomeprazole magnesium enteric coated preparation, finely ground, weigh finely ground esomeprazole magnesium enteric coated preparation powder and add hydrogen
Sodium hydroxide solution, ultrasonic, add ethanol, continue ultrasonic, quantitatively dilute with sodium hydroxide solution, obtain solution I, filter, obtain filtrate
I, take filtrate I and quantitatively dilute with described dissolution medium, obtain solution II；Solution II is placed in 37 DEG C ± 0.5 DEG C water-bath, respectively at
Different time points sampling filtering, obtains the filtrate II of each time point, takes filtrate II and adds sodium hydroxide solution, taken filtrate II and hydrogen
The volume ratio of sodium hydroxide solution is 1:0.1-0.14, shakes up, and is the esomeprazole magnesium solution b of described each time point；Institute
The concentration stating sodium hydroxide solution is 0.01mol/L～1.0mol/L；
(3) preparation of reference substance solution
Take omeprazole reference substance, dissolve with ethanol, more quantitatively dilute with dissolution medium, pipette the solution after dilution, add hydrogen
Sodium hydroxide solution, shakes up, and is reference substance solution；The concentration of described sodium hydroxide solution is 0.1mol/L～0.5mol/L, institute
The volume ratio stating the solution after dilution and sodium hydroxide solution is 1:0.1-0.14；
(4) high performance liquid chromatography detection
Step I: detect need testing solution a and reference substance solution by high performance liquid chromatography, records need testing solution a
Main peak peak area AA masterPeak area A with the impurity peaks that relative retention time is 2.7A is miscellaneous；And the peak area of reference substance solution；
Step II: by high performance liquid chromatography, the esomeprazole magnesium solution b of each time point is detected, record each time
Point main peak peak area AB masterPeak area A with the impurity peaks that relative retention time is 2.7B is miscellaneous；Set up each time point relative retention time
It is the impurity peaks peak area A of 2.7B is miscellaneousValue added and main peak peak area AB masterReduced value between equation of linear regression y=kx+m
And its correlation coefficient r, wherein y is the reduced value of main peak peak area, and x is the value added of impurity peaks peak area；
According to the peak area A of the impurity peaks that relative retention time is 2.7 of record in step IA is miscellaneousAnd the linear regression of step II
Equation y=kx+m, is calculated the reduced value of the main peak peak area of need testing solution a, adds the main peak peak of record in step I
Area AA master, it is calculated the stripping quantity that esomeprazole magnesium is actual, and then obtains dissolution.
The assay method of esomeprazole magnesium enteric coated preparation dissolution the most according to claim 1, it is characterised in that institute
Stating esomeprazole magnesium enteric coated preparation is esomeprazole magnesium enteric-coated pellet capsule or esomeprazole magnesium enteric coated tablet.
The assay method of esomeprazole magnesium enteric coated preparation dissolution the most according to claim 1, it is characterised in that institute
State phosphate buffered solution or water that dissolution medium is pH5.5-7.0.
4., according to the assay method of the esomeprazole magnesium enteric coated preparation dissolution described in any one of claim 1-3, it is special
Levying and be, the chromatographic condition of the high performance liquid chromatography detection described in step (4) is:
Chromatographic column: C18 chromatographic column, specification is 5 μm, 4.6*150mm；Flowing phase: acetonitrile-phosphate buffered solution-water, described second
Nitrile, phosphate buffered solution are 33-37:48-52:13-17 with the volume ratio of water, and the pH of described phosphate buffered solution is 7.2-
7.4；Flow velocity: 0.7～0.9mL/min；Sample size: 20 μ L；Column temperature: 25 DEG C～35 DEG C；Detection wavelength: 302nm.
The assay method of esomeprazole magnesium enteric coated preparation dissolution the most according to claim 4, it is characterised in that institute
Stating acetonitrile, phosphate buffered solution is 35:50:15 with the volume ratio of water；The pH of described phosphate buffered solution is 7.3, and it is joined
Method processed, for taking 1mol/L sodium dihydrogen phosphate 10.5ml and 0.5mol/L disodium phosphate soln 60ml, is diluted with water to
1000ml, shakes up and get final product；Flow velocity: 0.8mL/min；Column temperature: 30 DEG C.
6., according to the assay method of the esomeprazole magnesium enteric coated preparation dissolution described in any one of claim 1-3, it is special
Levying and be, in step (1), the esomeprazole magnesium in esomeprazole magnesium enteric coated preparation with the proportioning of dissolution medium is
20mg:900-1000mL；The concentration of described sodium hydroxide solution is 0.25mol/L～0.5mol/L, taken filtrate and hydroxide
The volume ratio of sodium solution is 1:0.12.
7., according to the assay method of the esomeprazole magnesium enteric coated preparation dissolution described in any one of claim 1-3, it is special
Levying and be, ethanol described in step (2) is 7-8ml:100mg with the proportioning of esomeprazole magnesium enteric coated preparation powder, described
The magnesium enteric coated preparation powder 5mg/mL Han esomeprazole in solution I；Taken filtrate I is 1 with the volume ratio of gained solution II:
50。
8., according to the assay method of the esomeprazole magnesium enteric coated preparation dissolution described in any one of claim 1-3, it is special
Levying and be, described in step (2), the concentration of sodium hydroxide solution is 0.25mol/L～0.5mol/L, taken filtrate II and hydrogen-oxygen
The volume ratio changing sodium solution is 1:0.12.
9., according to the assay method of the esomeprazole magnesium enteric coated preparation dissolution described in any one of claim 1-3, it is special
Levying and be, in step (3) described reference substance solution, the content of omeprazole is 20 μ g/ml.
10., according to the assay method of the esomeprazole magnesium enteric coated preparation dissolution described in any one of claim 1-3, it is special
Levy and be, in step (4) described equation of linear regression y=kx+m, 1.0≤k≤5.0,20000≤m≤100000, correlation coefficient
R is more than 0.995.
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| CN107561195A (en) * | 2017-07-26 | 2018-01-09 | 郑州泰丰制药有限公司 | The preparation method of reference substance and need testing solution used in a kind of Omeprazole dissolution measure |
| CN107843668A (en) * | 2017-12-05 | 2018-03-27 | 上海信谊万象药业股份有限公司 | The assay method of drug content in a kind of omeprazole solid preparation |
| CN107957381A (en) * | 2017-12-13 | 2018-04-24 | 南京双科医药开发有限公司 | A kind of assay method of spirolactone Dissolution of Tablet |
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| CN113092614A (en) * | 2021-04-01 | 2021-07-09 | 海南海力制药有限公司 | Omeprazole enteric capsule impurity detection method and consistency evaluation method |
| CN113092614B (en) * | 2021-04-01 | 2022-12-13 | 海南海力制药有限公司 | Omeprazole enteric capsule impurity detection method and consistency evaluation method |
| CN118311216A (en) * | 2024-06-07 | 2024-07-09 | 湖南明瑞制药股份有限公司 | Rapid determination method for dissolution rate of sodium rabeprazole enteric-coated tablets |
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