CN107764910A - Content assaying method of the one planting sand storehouse than the bent pentahydrate capsule of Valsartan trisodium half - Google Patents
Content assaying method of the one planting sand storehouse than the bent pentahydrate capsule of Valsartan trisodium half Download PDFInfo
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- CN107764910A CN107764910A CN201710791265.1A CN201710791265A CN107764910A CN 107764910 A CN107764910 A CN 107764910A CN 201710791265 A CN201710791265 A CN 201710791265A CN 107764910 A CN107764910 A CN 107764910A
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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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- 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
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Abstract
The present invention discloses content assaying method of the planting sand storehouse than the bent pentahydrate capsule of Valsartan trisodium half, it is first to take Sha Ku more appropriate than the bent pentahydrate reference substance of Valsartan trisodium half, husky storehouse that concentration is 50 μ g/mL is made than the bent pentahydrate reference substance of Valsartan trisodium half, takes Sha Ku that husky storehouse that concentration is 50 μ g/mL is made than the bent pentahydrate test sample of Valsartan trisodium half than the bent pentahydrate capsule sample of Valsartan trisodium half；Then it is as follows to formulate high-efficient liquid phase chromatogram condition:C18Chromatographic column (4.6mm × 250mm, 5 μm), mobile phase are 0.2% diisopropyl amine aqueous solution-N methyl pyrrolidones, Detection wavelength 250nm, flow velocity 0.8mL/min, 30 DEG C of column temperature, the μ L of sample size 10；It is finally accurate respectively to draw reference substance and need testing solution injection liquid chromatograph, measure.Than the content assaying method of the bent pentahydrate capsule of Valsartan trisodium half, the assay method is convenient, accurate, reliable, can truly reflect the quality of product in a planting sand storehouse of the invention.
Description
Technical field
The present invention relates to field of medicaments, and in particular to be that a planting sand storehouse has than the bent pentahydrate capsule of Valsartan trisodium half
Imitate the content assaying method of composition.
Background technology
Sha Ku is than the bent pentahydrate of Valsartan trisodium half (Sacubitril and Valsartan Trisodium
Hemipentahydrate) for trisodium (4- [(1S, 3R) -1- ([1,1 '-biphenyl] -4- methylene) -4- ethyoxyl -3- methyl -
4- oxos butyl] amino } -4- ketobutyric acids) (N- valeryls-N- { [2 '-(1H- tetrazole -5- bases) [1,1 '-biphenyl] -4-
Base] methyl }-Valine) half pentahydrate, molecular weight is 1916.018g/mol, and structural formula is as follows：
Sha Ku than the bent pentahydrate of Valsartan trisodium half by enkephalinase inhibitor sand storehouse than bent (NEP inhibitor)-
Sacubitril and angiotensin ii receptor blocker (the receptor blocker of Angiotensin II)-Valsartan figured silk fabrics
Sha Tan is with 1:1 equimolecular mol ratio forms, and is that an oral bio is effective, angiotensin receptor-enkephalins of double action
Enzyme inhibitor (angiotensin receptor-neprilysin inhibitor), for treating hypertension and heart failure,
With the cardiovascular death for heart failure patient of reducing risks and hospitalization chronic heart failure (NYHAII-IV levels) and penetrate blood system
Number reduces.The medicine is succeeded in developing by Nova Lab SDN. BHD, and being that European Union's Drug Administration is first in history harvests Accelerated evaluation money
The cardiovascular drugs of lattice, qualification was evaluated by U.S. FDA granted priority in 2 months 2015, for the heart failure reduced with LVEF
Treatment.
At present, Sha Ku is a kind of cardiovascular drug known to the public than the bent pentahydrate of Valsartan trisodium half.It is but existing
In technology, content assaying method of the rare husky storehouse of report than the bent pentahydrate capsule of Valsartan trisodium half.And pharmaceutical preparation is used as,
Content when strictly controlling it to dispatch from the factory is very necessary.The present invention exists to solve husky storehouse than the bent pentahydrate of Valsartan trisodium half
A kind of the problem of dispatching from the factory or being detected using preceding active constituent content, there is provided convenient, accurate, efficient and cheap detection method.
The content of the invention
It is an object of the invention to provide a planting sand storehouse containing than the bent pentahydrate capsule of Valsartan trisodium half
Quantity measuring method, the assay method is convenient, accurate, reliable, can truly reflect the quality of product.
In order to reach above-mentioned purpose, solution of the invention is：
One planting sand storehouse is than the content assaying method of the bent pentahydrate capsule of Valsartan trisodium half, including following step
Suddenly：
(1) preparation of reference substance：Take Sha Ku more appropriate than the bent pentahydrate reference substance of Valsartan trisodium half；
(2) preparation of test sample：Sha Ku is taken than the bent pentahydrate capsule sample 10~15mg of content of Valsartan trisodium half,
Filtrate is extracted to obtain with methanol, takes filtrate to be placed in standby in volumetric flask；
(3) high-efficient liquid phase chromatogram condition：C184.6mm × 250mm, 5 μm of chromatographic columns, mobile phase are 0.2% diisopropylamine
The aqueous solution -1-METHYLPYRROLIDONE, Detection wavelength 250nm；Flow velocity is 0.8mL/min, and column temperature is 30 DEG C, and sample size is 10 μ
L；
(4) determination method：Precision draws reference substance and need testing solution injection liquid chromatograph, measure.
In step (1), the husky storehouse is 50ug/mL than the concentration of the bent pentahydrate reference substance of Valsartan trisodium half.
In step (2), the husky storehouse is first placed in 20mL than the bent pentahydrate capsule sample content of Valsartan trisodium half
In volumetric flask, adding methanol to dissolve, ultrasonic 5min, filter, filtrate is let cool to room temperature, and then plus the mobile phase is diluted to scale,
Mixed liquor is shaken up, precision measures 1mL mixed liquors and put in 10mL measuring bottles, finally with methanol dilution to scale, shakes up, produces the confession
Test product.
In step (2), the husky storehouse is first placed in 20mL than the bent pentahydrate capsule sample content of Valsartan trisodium half
In volumetric flask, add methanol shaking dissolving, filtering, filtrate is let cool to room temperature, and then plus the mobile phase is diluted to scale, shakes up mixed
Liquid is closed, precision measures 1mL mixed liquors and put in 10mL measuring bottles, finally with methanol dilution to scale, shakes up, produce the test sample.
In step (3), the pH value of the mobile phase is 2.0~4.0, the mobile phase acid for adjusting pH value, preferably pH
Value 3.0, the diisopropyl amine aqueous solution of mobile phase 0.2% -1-METHYLPYRROLIDONE=60:40, the acid includes but unlimited
In for phosphoric acid, acetic acid, butenoic acid, formic acid, citric acid, tartaric acid, hydrogen sulfate receive, potassium acid sulfate, hydrochloric acid, sulfuric acid, carbonic acid, high chlorine
Acid, malic acid, citric acid, salicylic acid or caffeic acid, preferably phosphoric acid, acetic acid, butenoic acid, formic acid, citric acid, tartaric acid, sulfuric acid
Hydrogen receives or potassium acid sulfate, most preferably butenoic acid.The concentration of the butenoic acid is 5-20%, preferred concentration 10%.In the present invention
Preferable 10% butenoic acid can make Sha Ku have good separation than each chromatographic peak in the bent pentahydrate capsule of Valsartan trisodium half,
Improve peak conditions of streaking.
In step (4), the husky storehouse of the measure is not less than 73.5mg/ grains than the bent pentahydrate content of Valsartan trisodium half.
Assay side of the optimal planting sand storehouse of the invention than the bent pentahydrate capsule of Valsartan trisodium half
Method, comprise the following steps：
(1) preparation of reference substance：It is more appropriate than the bent pentahydrate reference substance of Valsartan trisodium half that precision weighs Sha Ku, adds methanol
Every lml is made containing solution of the husky storehouse than the bent μ g of half pentahydrate of Valsartan trisodium 50；
(2) preparation of test sample：Sha Ku is taken to put finely ground mistake in mortar than bent half pentahydrate capsule of Valsartan trisodium 20
No. four sieves, take Sha Ku is more appropriate than the bent pentahydrate capsule sample content of Valsartan trisodium half (it is more husky than bent figured silk fabrics to be approximately equivalent to Sha Ku
The smooth pentahydrate 10mg of trisodium half), it is accurately weighed, put in 20mL volumetric flasks, add methanol shaking to make dissolving, filter, filtrate lets cool
To room temperature, add the diisopropyl amine aqueous solution of mobile phase 0.2% -1-METHYLPYRROLIDONE to be diluted to scale, shake up, precision measures
1mL is put in 10mL volumetric flasks, with methanol dilution to scale, is shaken up, as need testing solution；
(3) high-efficient liquid phase chromatogram condition：
Chromatographic column：OJ-RH C18Chromatographic column (4.6mm × 250mm, 5 μm)；Mobile phase：0.2% diisopropyl
Base amine aqueous solution -1-METHYLPYRROLIDONE=60:40, with 10% butylene acid for adjusting pH value to 3.0；Detection wavelength：250nm；Stream
Speed:0.8mL/min；Column temperature：30℃；Sample size：10μL；Number of theoretical plate by husky storehouse than the bent pentahydrate peak of Valsartan trisodium half based on
6000 should be not less than by calculating；Input mode：Auto injection；
(4) determination method：It is accurate respectively to draw reference substance solution and each 10 μ L of need testing solution, liquid chromatograph is injected, is surveyed
It is fixed, produce.
In order to prove assay of the planting sand storehouse of the invention than the bent pentahydrate capsule of Valsartan trisodium half
Method accurately and reliably, is verified by following test method.
1st, instrument and reagent
Reagent used in the present invention can from the market be bought or can be by method system described in the invention
It is standby and obtain.
Reagent：1-METHYLPYRROLIDONE, water are chromatographically pure, and butenoic acid, diisopropyl amine solution are that analysis is pure.
Sample：Beijing Rundekang Medical Technology Co., Ltd provides.
Reference substance：Sha Ku is than the bent pentahydrate reference substance (lot number of Valsartan trisodium half：J08373P1) had by Novartis
Limit company provides, for assay.
Instrument：The high performance liquid chromatographs of Agilent 1100 (Agilent companies), DV215CD electronic balances (OHaus
Discovery companies), UV-1750 ultraviolet-uisible spectrophotometers (Japanese Shimadzu Corporation), 410HT- ultrasonic washing instruments are (extensively
Xing Shuo Instrument Ltd. of state city).
2nd, chromatographic condition
Chromatographic column：OJ-RH C18Chromatographic column (4.6mm × 250mm, 5 μm)；Mobile phase：0.2% diisopropyl
Base amine aqueous solution -1-METHYLPYRROLIDONE=60:40, with 10% butylene acid for adjusting pH value to 3.0；Detection wavelength：250nm；Stream
Speed:0.8mL/min；Column temperature：30℃；Sample size：10μL；Number of theoretical plate by husky storehouse than the bent pentahydrate peak of Valsartan trisodium half based on
6000 should be not less than by calculating；Input mode：Auto injection.
3rd, the preparation of reference substance solution：It is more appropriate than the bent pentahydrate reference substance of Valsartan trisodium half that precision weighs Sha Ku, adds
Every lml is made containing solution of the husky storehouse than the bent μ g of half pentahydrate of Valsartan trisodium 50 in methanol.
4th, the preparation of need testing solution：Sha Ku is taken to put in mortar and grind than bent half pentahydrate capsule of Valsartan trisodium 20
It is thin to cross No. four sieves, take Sha Ku is more appropriate than the bent pentahydrate capsule sample content of Valsartan trisodium half (to be approximately equivalent to Sha Ku than bent
The pentahydrate 10mg of Valsartan trisodium half), it is accurately weighed, put in 20mL volumetric flasks, add methanol shaking to make dissolving, filter, filtrate
Let cool to room temperature, add mobile phase to be diluted to scale, shake up, precision measures 1mL and put in 10mL volumetric flasks, with methanol dilution to quarter
Degree, shakes up, and produces and husky storehouse of the concentration for 50 μ g/mL is made than the bent pentahydrate need testing solution of Valsartan trisodium half.
5th, determination method：It is accurate respectively to draw reference substance solution and each 10 μ L of need testing solution, liquid chromatograph is injected, is surveyed
It is fixed, produce.
6th, negative sample interference determines：
Prepared by husky storehouse than the bent pentahydrate capsule prescription of Valsartan trisodium half and lack Sha Ku than bent Valsartan trisodium half
The negative sample of pentahydrate, according to above-mentioned husky storehouse than test sample under the bent pentahydrate capsule assay item of Valsartan trisodium half
The preparation method of solution prepares negative control solution, is surveyed according to above-mentioned husky storehouse than the bent pentahydrate capsule agent content of Valsartan trisodium half
Determine the determination method measure under item, record chromatogram (such as Fig. 1).As a result show, in Sha Ku than the bent pentahydrate of Valsartan trisodium half
At (lactose, microcrystalline cellulose, sodium carboxymethylcellulose, lauryl sodium sulfate, magnesium stearate and PVP etc.) appearance, prescription
In other auxiliary materials occur without peak, therefore auxiliary material does not disturb husky storehouse than the assay of the bent pentahydrate of Valsartan trisodium half.
7th, the investigation of linear relationship
Precision weighs Sha Ku than the bent pentahydrate of Valsartan trisodium half about 20mg, accurately weighed, is placed in 20mL volumetric flasks,
Add methanol shaking to make dissolving and be diluted to scale, shake up, precision measures 10mL and is placed in 100mL volumetric flasks, with methanol dilution extremely
Scale, shake up, as storing solution.
Precision measures storing solution 1mL, 2mL, 5mL, 10mL, 12mL, 15mL and is respectively placed in 20mL volumetric flasks, with 50% second
The nitrile aqueous solution is diluted to scale, shakes up, as linear need testing solution.With Sha Ku than the bent pentahydrate peak face of Valsartan trisodium half
Product (A) is ordinate, and Sha Ku is abscissa than the bent pentahydrate solution concentration (C) of Valsartan trisodium half, obtains Sha Ku than bent figured silk fabrics
Regression equation A=15128C+3.4183 (the R of husky smooth half pentahydrate of trisodium-Valsartan2=0.9999, Fig. 2-A), Sha Ku ratios
Regression equation A=25460C+6.8811 (the R bent bent pentahydrate-Sha Kubi of Valsartan trisodium half2=0.9999, Fig. 2-B),
As a result show, Valsartan is linear good in the range of 0.0025~0.0374mg/mL, Sha Ku than it is bent 0.0023~
Linear good in the range of 0.0349mg/mL, Sha Ku is than the bent pentahydrate of Valsartan trisodium half in 0.0023~0.0349mg/mL models
Enclose interior linear good.
8th, strong Degrading experiment
Take Sha Ku more appropriate than the bent pentahydrate reference substance of Valsartan trisodium half, tested under the following conditions respectively:(1)
Alkali destroys：0.1mol/L sodium hydroxide solutions are added to make dissolving in right amount, room temperature is placed 0.5 hour, and acid adding neutralizes, and adds mobile phase to rule
Volume is determined, as alkaline degradation product solution；(2) acid destroys：0.1mol/L hydrochloric acid solutions are added to make dissolving in right amount, it is small that room temperature places 2
When, add alkali to neutralize, add mobile phase to prescribed volume, as acid degradation reaction mixture；(3) high temperature：2 are placed in 80 DEG C of water-baths
Hour, let cool to room temperature, scale is diluted to mobile phase, as high temperature degradation reaction mixture；(4) photo damage：Put under illumination meter
Place 12 hours, scale is diluted to mobile phase, as Photodegradation Products solution；(5) Oxidative demage：Add 30% hydrogen peroxide 1mL,
After placing about 2 hours, scale is diluted to mobile phase, as Oxidative demage reaction mixture.Enter respectively under above-mentioned chromatographic condition
Row measure.As shown in figure 3, husky storehouse is destroyed than the bent pentahydrate of Valsartan trisodium half through acid, alkali, oxidation, high temperature, illumination, figured silk fabrics is husky
Smooth to be met the requirements with husky storehouse than bent peak peak purity, catabolite peak does not disturb the measure of principal component.
9th, stability experiment
Sha Ku is taken, according to content assaying method processing, to be prepared than the bent pentahydrate capsule about 10mg of Valsartan trisodium half for examination
Product solution, measure is sampled respectively at 0,1,2,3,4,5,6,7,8,9,10h according to content assaying method, records chromatogram.Knot
Fruit is shown in Table 1, and need testing solution room temperature places about 10h, and Valsartan peak is less than 2% than bent peak peak area rate of change with husky storehouse, shown
It is stable that this product places 10h at ambient temperature.
1 husky storehouse of table is than the bent pentahydrate capsule solution stability experiment result of Valsartan trisodium half
10th, repeated experiment
Take with a collection of husky storehouse than the bent pentahydrate capsule of Valsartan trisodium half, prepare and supply by the preparation method of need testing solution
6 parts of test sample solution, assay is carried out, record chromatogram, husky storehouse is calculated than the hydration of bent Valsartan trisodium half five according to external standard method
The content of thing.2 are the results are shown in Table, 6 parts of test sample sand storehouses are 98.6% than the average content of bent Valsartan under this chromatographic condition,
RSD (n=6) is 0.49%；As a result show that method repeatability is good.
2 husky storehouse of table is than the bent pentahydrate capsule content repeated experiment result of Valsartan trisodium half
11st, the rate of recovery is tested
Precision weighs Sha Ku and is placed in 20mL volumetric flasks than the bent pentahydrate of Valsartan trisodium half about 8mg, 10mg, 12mg respectively
In, add methanol shaking to make dissolving, and scale is diluted to, shake up, then precision measures 1mL and is placed in 10mL volumetric flasks, it is dilute with methanol
Release to scale, shake up, the need testing solution as 80%, 100%, 120% concentration.Each concentration is parallel to prepare 3 parts, by content
Assay method measure content record chromatogram.
Precision weighs Sha Ku ratios song respectively and each about 10mg of Valsartan reference substance is put in 20mL measuring bottles, adds mobile phase shaking to make
Dissolving, and scale is diluted to, shake up, then precision measures 1mL and is placed in 10mL volumetric flasks, is diluted to scale with mobile phase, shakes up,
As reference substance solution.Each concentration is parallel to prepare 3 parts, by content assaying method measure content record chromatogram.
The results are shown in Table 3 and table 4, under the chromatographic condition drafted, Sha Ku than bent half pentahydrate of Valsartan trisodium two into
The average recovery rate of swarming is between 98.0%~101.0%, and RSD values are less than 1.0%, and the rate of recovery meets regulation.
3 husky storehouse of table is than half pentahydrate of bent Valsartan trisodium-Valsartan accuracy result
4 husky storehouse of table is than the bent pentahydrate-Sha Kubi song accuracy results of Valsartan trisodium half
12nd, serviceability test
In Detection wavelength 250nm ± 2nm, flow velocity 1.0mL/min ± 0.1mL/min, 30 DEG C ± 5 DEG C of column temperature, mobile phase pH
3.0 ± 0.1, husky storehouse is determined than the hydration of bent Valsartan trisodium half five under conditions of watr-proportion 50% ± 5% and different chromatographic columns
The content of thing, the results showed that the RSD of the data under each change condition in triplicate is respectively less than 2%, the durability of chromatographic condition
Well.
13rd, Intermediate precision is tested
Prepare test sample and reference substance solution on different tests instrument by different tests personnel, precision measure test sample and
The μ L of reference substance solution 10 inject liquid chromatograph, continuous sample introduction 6 times, record chromatogram.With 6 parts in 10, repeated experiment for trying
The content data of product solution merges and compared, and Valsartan, Sha Ku are than bent, Sha Ku than the bent pentahydrate content of Valsartan trisodium half
RSD values are respectively 0.66%, 0.64%, 0.59%.In same laboratory, through different time, different analysis personnel, distinct device
Determination sample, sample tests are more or less the same.
To sum up, assay side of the planting sand storehouse of the invention than the bent pentahydrate capsule of Valsartan trisodium half
Method, the assay method is convenient, accurate, reliable, can truly reflect the quality of product.
Brief description of the drawings
Fig. 1 is the experimental patterns of negative sample interference measure, and Y-axis is peak intensity, and X-axis is appearance time, wherein Fig. 1
(A) negative sample is corresponded to, Fig. 1 (B) corresponds to reference substance；
Fig. 2 is the linear collection of illustrative plates of test example linear regression fit, and wherein Fig. 2 (A) corresponds to Sha Ku than bent Valsartan trisodium
The linear collection of illustrative plates of half pentahydrate-Valsartan, it is more bent than the bent pentahydrate-Sha Kubi of Valsartan trisodium half that Fig. 2 (B) corresponds to Sha Ku
Linear collection of illustrative plates；
Fig. 3 is the chromatogram collection of illustrative plates of the strong Degrading experiment of test example, and Y-axis is peak intensity, and X-axis is appearance time, wherein Fig. 3
(A) corresponding alkali is destroyed, and Fig. 3 (B) relative acid is destroyed, the corresponding high temperatures of Fig. 3 (C), the corresponding photo damages of Fig. 3 (D), and Fig. 3 (E) is corresponding
Oxidative demage.
Embodiment
In order to which technical scheme is explained further, the present invention is explained in detail below by specific embodiment
State.
Embodiment 1
One planting sand storehouse is than the content assaying method of the bent pentahydrate capsule of Valsartan trisodium half, including following step
Suddenly：
(1) preparation of reference substance：It is more appropriate than the bent pentahydrate reference substance of Valsartan trisodium half that precision weighs Sha Ku, adds methanol
Every lml is made containing solution of the husky storehouse than the bent μ g of half pentahydrate of Valsartan trisodium 50；
(2) preparation of test sample：Different batches sand storehouse is taken to put mortar than bent half pentahydrate capsule of Valsartan trisodium 20
In No. four sieves of finely ground mistake, take Sha Ku (to be approximately equivalent to Sha Ku in right amount than the bent pentahydrate capsule sample content of Valsartan trisodium half
Than the bent pentahydrate 10mg of Valsartan trisodium half), it is accurately weighed, put in 20mL volumetric flasks, add methanol shaking to make dissolving, filter,
Filtrate is let cool to room temperature, adds mobile phase to be diluted to scale, is shaken up, and precision measures 1mL and put in 10mL volumetric flasks, with methanol dilution extremely
Scale, shake up, as need testing solution；
(3) high-efficient liquid phase chromatogram condition：
Chromatographic column：OJ-RH C18Chromatographic column (4.6mm × 250mm, 5 μm)；Mobile phase：0.2% diisopropyl
Base amine aqueous solution -1-METHYLPYRROLIDONE=60:40, with 10% butylene acid for adjusting pH value to 3.0；Detection wavelength：250nm；Stream
Speed:0.8mL/min；Column temperature：30℃；Sample size：10μL；Number of theoretical plate by husky storehouse than the bent pentahydrate peak of Valsartan trisodium half based on
6000 should be not less than by calculating；Input mode：Auto injection；
(4) determination method：It is accurate respectively to draw reference substance solution and each 10 μ L of need testing solution, liquid chromatograph is injected, is surveyed
It is fixed, Valsartan in each batch need testing solution, Sha Ku are calculated than bent, Sha Ku than the bent pentahydrate of Valsartan trisodium half by external standard method
Content, as a result as shown in table 5.
5 husky storehouse of table is than the bent pentahydrate capsule content testing result of Valsartan trisodium half
Above-described embodiment and schema and non-limiting product form of the invention and style, any art it is common
The appropriate change or modification that technical staff is done to it, it all should be regarded as not departing from the patent category of the present invention.
Claims (7)
1. a planting sand storehouse is than the content assaying method of the bent pentahydrate capsule of Valsartan trisodium half, it is characterised in that：
Comprise the following steps：
(1) preparation of reference substance：Take Sha Ku more appropriate than the bent pentahydrate reference substance of Valsartan trisodium half；
(2) preparation of test sample：Sha Ku is taken to use first than the bent pentahydrate capsule sample 10~15mg of content of Valsartan trisodium half
Alcohol extracting obtains filtrate, takes filtrate to be placed in standby in volumetric flask；
(3) high-efficient liquid phase chromatogram condition：C184.6mm × 250mm, 5 μm of chromatographic columns, mobile phase are that 0.2% diisopropylamine is water-soluble
Liquid -1-METHYLPYRROLIDONE, Detection wavelength 250nm；Flow velocity is 0.8mL/min, and column temperature is 30 DEG C, and sample size is 10 μ L；
(4) determination method：Precision draws reference substance and need testing solution injection liquid chromatograph, measure.
2. planting sand storehouse according to claim 1 is than the bent pentahydrate capsule of Valsartan trisodium half containing measurement
Determine method, it is characterised in that：In step (1), the husky storehouse is than the concentration of the bent pentahydrate reference substance of Valsartan trisodium half
50ug/mL。
3. planting sand storehouse according to claim 1 is than the bent pentahydrate capsule of Valsartan trisodium half containing measurement
Determine method, it is characterised in that：In step (2), first by the husky storehouse than the bent pentahydrate capsule sample content of Valsartan trisodium half
Thing is placed in 20mL volumetric flasks, adds methanol to dissolve, ultrasonic 5min, filtering, and filtrate is let cool to room temperature, and then plus the mobile phase is dilute
To release to scale, shake up mixed liquor, precision measures 1mL mixed liquors and put in 10mL measuring bottles, finally with methanol dilution to scale, shakes up,
Produce the test sample.
4. planting sand storehouse according to claim 1 is than the bent pentahydrate capsule of Valsartan trisodium half containing measurement
Determine method, it is characterised in that：In step (2), first by the husky storehouse than the bent pentahydrate capsule sample content of Valsartan trisodium half
Thing is placed in 20mL volumetric flasks, adds methanol shaking dissolving, filtering, and filtrate is let cool to room temperature, and then plus the mobile phase is diluted to
Scale, mixed liquor is shaken up, precision measures 1mL mixed liquors and put in 10mL measuring bottles, finally with methanol dilution to scale, shakes up, produces
The test sample.
5. planting sand storehouse according to claim 1 is than the bent pentahydrate capsule of Valsartan trisodium half containing measurement
Determine method, it is characterised in that：In step (3), the pH value of the mobile phase is 2.0~4.0, the mobile phase acid for adjusting pH
Value, the acid includes but is not limited to for phosphoric acid, acetic acid, butenoic acid, formic acid, citric acid, tartaric acid, hydrogen sulfate are received, potassium acid sulfate,
Hydrochloric acid, sulfuric acid, carbonic acid, perchloric acid, malic acid, citric acid, salicylic acid or caffeic acid.
6. planting sand storehouse according to claim 5 is than the bent pentahydrate capsule of Valsartan trisodium half containing measurement
Determine method, it is characterised in that：The acid is 10% butenoic acid.
7. planting sand storehouse according to claim 1 is than the bent pentahydrate capsule of Valsartan trisodium half containing measurement
Determine method, it is characterised in that：The mobile phase is 0.2% diisopropyl amine aqueous solution -1-METHYLPYRROLIDONE=60:40
Mobile phase.
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|---|---|---|---|
| CN201710791265.1A CN107764910B (en) | 2017-09-05 | 2017-09-05 | Method for measuring content of active ingredients of Sacubitril valsartan trisodium semipentahydrate capsule |
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| CN201710791265.1A CN107764910B (en) | 2017-09-05 | 2017-09-05 | Method for measuring content of active ingredients of Sacubitril valsartan trisodium semipentahydrate capsule |
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| CN109239214A (en) * | 2018-09-19 | 2019-01-18 | 珠海润都制药股份有限公司 | One seed sand library is than library husky in bent sodium than the bent isomers method of inspection |
| CN111077232A (en) * | 2018-10-18 | 2020-04-28 | 珠海润都制药股份有限公司 | Inspection method of Sacubitril valsartan sodium related substances |
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| WO2014126979A1 (en) * | 2013-02-14 | 2014-08-21 | Novartis Ag | Substituted bisphenyl butanoic phosphonic acid derivatives as nep (neutral endopeptidase) inhibitors |
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| CN109239214A (en) * | 2018-09-19 | 2019-01-18 | 珠海润都制药股份有限公司 | One seed sand library is than library husky in bent sodium than the bent isomers method of inspection |
| CN111077232A (en) * | 2018-10-18 | 2020-04-28 | 珠海润都制药股份有限公司 | Inspection method of Sacubitril valsartan sodium related substances |
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