CN107907603A - A kind of measure assay method of the amino acids parenteral solution tryptophan in relation to material - Google Patents
A kind of measure assay method of the amino acids parenteral solution tryptophan in relation to material Download PDFInfo
- Publication number
- CN107907603A CN107907603A CN201711050017.8A CN201711050017A CN107907603A CN 107907603 A CN107907603 A CN 107907603A CN 201711050017 A CN201711050017 A CN 201711050017A CN 107907603 A CN107907603 A CN 107907603A
- Authority
- CN
- China
- Prior art keywords
- tryptophan
- mobile phase
- relation
- amino acids
- parenteral solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/34—Control of physical parameters of the fluid carrier of fluid composition, e.g. gradient
-
- 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
- G01N30/62—Detectors specially adapted therefor
- G01N30/74—Optical detectors
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)
- Spectroscopy & Molecular Physics (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Indole Compounds (AREA)
Abstract
The present invention provides a kind of measure assay method of the amino acids parenteral solution tryptophan in relation to material, is related to pharmaceutical technology field；The assay method is used to measure content of the tryptophan in relation to material in amino acids parenteral solution, and the method uses high performance liquid chromatography, uses chromatographic column of the octadecylsilane chemically bonded silica for stationary phase, using three kinds of mobile phases：Mobile phase A is 0.01mol/L sodium dihydrogen phosphates, and PH=7.2 is adjusted with sodium hydroxide solution；Mobile phase B is acetonitrile, methanol, water are according to volume ratio 45:45:10 mixing gained；Mobile phase C is methanol, water is according to 10:90 volume ratio mixing gained, carry out gradient elution, analysis calculating is carried out in a manner of tryptophan relative retention time, separation determination is carried out to the related material of tryptophan in amino acid injection, assay method provided by the invention is fast with tryptophan Related substance speed, accuracy rate is high, the beneficial effects such as inspection cost is low.
Description
Technical field
The present invention provides a kind of measure assay method of the amino acids parenteral solution tryptophan in relation to material, is related to medical science
Field.
Background technology
Amino acid transfusion is various in style, and species, the quantity such as each kind is amino acid contained, electrolyte are different, and purposes is also
It is different, for clinically widely used nutrition treatment infusion products.Tryptophan is one of essential amino acid, can be converted into human body
A kind of important transmitter substance, that is, serotonin in brain, is one of main component in amino acid injection, due to color
Propylhomoserin is to sensitivities such as light, heat, oxygen, in the preparation process of amino acids parenteral solution, if rationally control Oxygen control process,
The links such as sterilization process, tryptophan is degradable to produce related material, and tryptophan degradation rate, that is, related material of tryptophan is in amino acid
Shared ratio in class parenteral solution, can reflect the quality of amino acids injection products.There is tryptophan in EP, USP pharmacopeia
Introduction in relation to material in bulk pharmaceutical chemicals, but document report of the tryptophan in relation to material is had no in amino acids parenteral solution.
The content of the invention
The present invention solves the skill of assay method of the tryptophan in relation to material in lack amino acid class parenteral solution in the prior art
Art problem, there is provided a kind of efficient, accurate high, low measure side of the measure amino acids parenteral solution tryptophan in relation to material of cost
Method, the method are as follows：Using high performance liquid chromatography, with the chromatographic column that octadecylsilane chemically bonded silica is stationary phase, press
Following mobile phase condition carries out gradient elution；Including three kinds of mobile phases, mobile phase A is 0.01mol/L sodium dihydrogen phosphates, uses hydrogen-oxygen
Change sodium solution and adjust PH=7.0~7.4；Mobile phase B is acetonitrile, methanol, water are according to volume ratio 45:45:10 mixing gained；Flowing
Phase C is methanol, water is according to 10:90 volume ratio mixing gained；The gradient of mobile phase sets as follows：
| Time (min) | Mobile phase A (%) | Mobile phase B (%) | Mobile phase C (%) | Flow velocity (ml/min) |
| 0 | 100 | 0 | 0 | 1.2 |
| 30 | 45 | 55 | 0 | 1.2 |
| 35 | 0 | 100 | 0 | 1.2 |
| 35.5 | 0 | 0 | 100 | 1.2 |
| 36 | 0 | 0 | 100 | 1.5 |
| 40 | 0 | 0 | 100 | 1.5 |
| 42.5 | 100 | 0 | 0 | 1.5 |
| 45 | 100 | 0 | 0 | 1.2 |
| 48 | 100 | 0 | 0 | 1.2 |
As further preferred, the column temperature is 40 DEG C, Detection wavelength 220nm.
As further preferred, the PH of the mobile phase A is 7.2.
The present invention is established by using for reference in EP, BP, USP pharmacopeia the detection method in relation to material in tryptophan bulk pharmaceutical chemicals
Analysis determining method of the tryptophan in relation to material in a kind of amino acids parenteral solution.Using acetyltryptophan as certainly in analytic process
Body compares, and analysis calculating is carried out in a manner of tryptophan relative retention time, it is specified that the sum of impurity peak area is not greater than acetyl
5 times (1.0%) of tryptophan product peak area.By methodology validation, its result is good, can effectively measure amino acids
Parenteral solution (Amino Acid Compound Injection (18AA), Amino Acid Compound Injection (18AA-II), moriamin-s
(17AA), amino acid (15) double peptides (2) parenteral solution etc.) in the related material of tryptophan, monitor oxygen control in its preparation process
Process processed, sterilization process etc., reflect the quality of final product quality.
Brief description of the drawings
Fig. 1 methionine chromatograms；
Fig. 2 (hydrochloric acid) histidine chromatogram；
Fig. 3 L-aminobutanedioic acid chromatograms；
Fig. 4 alanine chromatograms；
Fig. 5 valine chromatograms；
Fig. 6 (hydrochloric acid) lysine chromatogram；
Fig. 7 leucine chromatograms；
Fig. 8 threonine chromatograms；
Fig. 9 tyrosine chromatograms；
Figure 10 (hydrochloric acid) arginine chromatogram；
Figure 11 isoleucine chromatograms；
Figure 12 proline chromatograms；
Figure 13 phenylalanine chromatograms；
Figure 14 glycine chromatograms；
Figure 15 serine chromatograms；
Figure 16 glutamic acid chromatograms；
Figure 17 tryptophan chromatograms；
The related material chromatogram of Figure 18 Amino Acid Compound Injections (18AA) tryptophan；
The related material chromatogram of Figure 19 Amino Acid Compound Injections (18AA-2) tryptophan；
The related material chromatogram of Figure 20 amino acids (15) double peptides (2) parenteral solution tryptophan；
Specific embodiment
Form by the following examples, to the present invention relates to the related material detection side of measure amino acids parenteral solution tryptophan
Method is described in further detail, but the scope that this should not be interpreted as to the above-mentioned theme of the present invention is only limitted to following example, all
The technology realized based on the above of the present invention belongs to the scope of the present invention.
Embodiment 1
Take this product direct injected；It is appropriate that another precision weighs tryptophan product, is made with water in every 1ml containing about 0.9mg's
Solution.It is filler with octadecylsilane chemically bonded silica according to high effective liquid chromatography for measuring, as the chromatographic column of stationary phase,
Acetyltryptophan is selected as own control to detect the related material of tryptophan, mobile phase includes three kinds, and mobile phase A is
0.01mol/L sodium dihydrogen phosphates, and pH=7.2 is adjusted with sodium hydroxide solution, Mobile phase B is acetonitrile, methanol, water are according to 45：
45：10 volume ratio mixing gained, mobile phase C is methanol, water is according to 10：90 volume ratio mixing gained, 40 DEG C of column temperature, detection
Wavelength is 220nm；According to the form below carries out gradient elution.
| Time (min) | Mobile phase A (%) | Mobile phase B (%) | Mobile phase C (%) | Flow velocity (ml/min) |
| 0 | 100 | 0 | 0 | 1.2 |
| 30 | 45 | 55 | 0 | 1.2 |
| 35 | 0 | 100 | 0 | 1.2 |
| 35.5 | 0 | 0 | 100 | 1.2 |
| 36 | 0 | 0 | 100 | 1.5 |
| 40 | 0 | 0 | 100 | 1.5 |
| 42.5 | 100 | 0 | 0 | 1.5 |
| 45 | 100 | 0 | 0 | 1.2 |
| 48 | 100 | 0 | 0 | 1.2 |
Precision measures above-mentioned test solution and each 20 μ l of tryptophan product solution, injects liquid chromatograph, records color
Spectrogram；Another to weigh that acetyltryptophan reference substance is appropriate, being dissolved in water and being diluted to is made solution conducts of every 1ml containing about 2.0 μ g
Contrast solution, is measured in the same method.Disregard at peak in chromatogram before 0.54 times of tryptophan relative retention time；After the time, remove
, must not be big if any the sum of impurity peaks, its peak area before 30min outside the peak and tryptophan peak that 0.78 times of tryptophan relative retention time
In 5 times (1.0%) of acetyltryptophan reference substance peak area.It is any in test solution to be less than acetyltryptophan contrast solution master
The peak that 0.1 times of peak area can be neglected.
Related material, that is, the impurity of tryptophan in embodiment, the calculation formula of proportion is in amino acids parenteral solution：rU：The tryptophan impurity gross area in test solution；rS：Acetyltryptophan peak face
Product；cS：Acetyltryptophan concentration (mg/ml)；cU：The prescription strength of tryptophan.
The following items of assay method of the amino acids parenteral solution tryptophan in relation to material are verified below：
1. the confirmation of tryptophan relative retention time
18 kinds of Freamine Ⅲs of recipe quantity are prepared, according to the liquid-phase condition sample introduction described in embodiment, chromatogram is shown in attached
Fig. 1-17, statistical content are shown in Table 1 and table 2.
1 18 kinds of amino acid retention times of table
| Project | Retention time |
| Cystine | Non- appearance |
| (hydrochloric acid) lysine | 2.108 |
| L-aminobutanedioic acid | 2.115 |
| Glutamic acid | 2.141 |
| Serine | 2.193 |
| Glycine | 2.182 |
| Alanine | 2.236 |
| Threonine | 2.300 |
| (hydrochloric acid) arginine | 2.329 |
| (hydrochloric acid) histidine | 2.649 |
| Proline | 2.682 |
| Valine | 3.252 |
| Methionine | 4.322 |
| Isoleucine | 5.582 |
| Tyrosine | 5.655 |
| Leucine | 5.833 |
| Phenylalanine | 8.851 |
| Tryptophan | 11.328 |
The relative retention time table of 2 tryptophan of table and methionine etc.
| Contrast project | Tryptophan relative retention time |
| Isoleucine | 0.493 |
| Tyrosine | 0.499 |
| Leucine | 0.515 |
| Phenylalanine | 0.781 |
From the content of Tables 1 and 2 can be seen that peak in chromatogram before 0.54 times of tryptophan relative retention time,
The peak (phenylalanine) that 0.78 times of tryptophan relative retention time is negative sample peak, does not contain the related material of tryptophan.From
Peak after 0.54 times of tryptophan relative retention time, removes the peak and tryptophan peak of 0.78 times of tryptophan relative retention time,
For the related material of tryptophan, tryptophan can be calculated in relation to the material i.e. gross area of impurity, so as to apply mechanicallyFormula obtains tryptophan impurity %, so as to reflect the quality of test sample quality.
2. the selection of own control thing
Detection method of the tryptophan bulk pharmaceutical chemicals in relation to material inside USP, BP, EP, use by the use of acetyltryptophan as
Own control detects the related material of tryptophan.
Under the liquid-phase condition of embodiment 1, the tryptophan peak area of 2 μ g/ml is the acetyltryptophan of 307469,2 μ g/ml
Peak area is 241138；From the point of view of above test data, can select acetyltryptophan as the present embodiment own control more
To be stringent.
3. methodological study
(1) chromatographic condition and system suitability
It is prepared by system suitability solution：Take acetyltryptophan reference substance appropriate, every 1ml is made containing about 2.0 μ g acetyl color ammonia
The solution of acid is as system suitability solution.
Operating method：Said system applicability solution is taken, 20 μ l of sample introduction are detected, and are repeated six times, record chromatogram.Meter
The RSD for calculating acetyltryptophan peak peak area is 0.5%；The RSD of main peak retention time is 0.01%.
(2) specificity (interference test)
According in relation to the detection method under material item, aqueous, mobile phase solution, acetyltryptophan reference substance are molten respectively
Liquid, tryptophan product solution, negative solution (prepared according to prescription and be free of tryptophan) and each 20 μ l of formulation samples, inject liquid phase
Chromatograph, records chromatogram.
As a result prove that aqueous solution, mobile phase solution are noiseless to impurity research, and negative solution has interference, need to deduct sky
In vain.
(3) test limit
Acetyltryptophan contrast solution is diluted to various concentrations and is measured, with signal-to-noise ratio 3:1 is standard, at this time acetyl color
Propylhomoserin concentration is 0.51 μ g/ml.
(4) quantitative limit
Acetyltryptophan contrast solution is diluted to various concentrations and is measured, with signal-to-noise ratio 10:1 is standard, at this time acetyl
Tryptophan concentration is 1.82 μ g/ml.The test liquid of 6 parts of minimum quantitative limit concentration is prepared respectively into 1 pin, when acetyltryptophan peak retains
Between RSD should be 0.01%, the RSD of peak area is 0.5%.
(5) accuracy test
Precision weighs acetyltryptophan reference substance 10mg, 10mg, 10mg respectively；20mg、20mg、20mg；30mg、30mg、
30mg；9 100ml measuring bottles are put, add negative solution (to prepare and be free of tryptophan) dissolving according to prescription, constant volume, shake up.It is smart respectively again
Close measurement 1.00ml is placed in 9 100ml measuring bottles, adds negative solution (to prepare and be free of tryptophan) dissolving according to prescription, constant volume, shake
It is even, as accuracy solution to be measured.According in relation to the detection method under material item, measure in accordance with the law, record chromatogram, calculate the rate of recovery
With the relative standard deviation of the rate of recovery, the average recovery rate under each concentration should all be between 80%-120%.It the results are shown in Table 3：
3 acetyltryptophan accuracy test result of table
The result shows that：The average recovery rate of acetyltryptophan content assaying method is 108.1%, RSD 3.8%, is being marked
Accuracy is good in the range of the 50%~150% of the amount of showing.
(6) precision test-repetitive test, Intermediate precision experiment
Repetitive test：B1401001 batches of Amino Acid Compound Injections (18AA) are taken, according in relation to the detection side under material item
Method, takes stoste to be fitted into sample introduction in 6 liquid phase bottles, records chromatogram, calculates relative standard deviation, should be RSD≤15%.Taken with method
Stoste is fitted into sample introduction in 6 liquid phase bottles, is measured in accordance with the law on different instruments by different personnel, records chromatogram, calculates measure and contains
Measure relative standard deviation.For this experimental result compared with repeated experiment result, the RSD of 12 data of gained answers≤20%.
As a result record as shown in table 4 below：
The related material Precision test result of 4 tryptophan of table
As shown in Table 4：In repetitive test, 6 RSDs of the sample tryptophan in relation to substance-measuring are 12%, show originally to contain
The repeatability of quantity measuring method is good.In Intermediate precision experiment, 12 RSDs of the sample tryptophan in relation to substance-measuring are
12%, show that the Intermediate precision of this content assaying method is good.
(7) durability
1. the comparison of different column temperatures
B1401001 batches of Amino Acid Compound Injections (18AA) are taken, according in relation to the detection method under material item, other chromatographies
Condition is constant, and sample introduction when setting 36 DEG C, 39 DEG C and 42 DEG C of column temperature respectively, records chromatogram.Result of the test is shown in Table 5：
The result of the test that the related material of the different column temperature tryptophans of table 5 influences
The result shows that：Amino Acid Compound Injection (18AA) is under the different detection temperatures of the condition, the related thing of tryptophan
For the absolute value of matter within ± 0.1%, stability result is good.
2. the comparison of different mobile phase pH
B1401001 batches of Amino Acid Compound Injection (18AA) samples are taken, other chromatographic conditions are constant, set mobile phase A
Sample introduction when pH is respectively 7.0,7.2,7.4, records chromatogram.Result of the test is shown in Table 6：
The result of the test that the related material of the different mobile phase pH tryptophans of table 6 influences
The result shows that：Amino Acid Compound Injection (18AA) is under the different mobile phase pH of the condition, the related thing of tryptophan
For the absolute value of matter within ± 0.1%, stability result is good.
3. the comparison of different Detection wavelengths
B1401001 batches of Amino Acid Compound Injection (18AA) samples are taken, other chromatographic conditions are constant, set Detection wavelength
Respectively 215nm, 220nm, 225nm when sample introduction, record chromatogram.Stability test the results are shown in Table 7：
The result of the test that the related material of the different Detection wavelength tryptophans of table 7 influences
The result shows that：Amino Acid Compound Injection (18AA) is under the different Detection wavelengths of the condition, the related thing of tryptophan
For the absolute value of matter within ± 0.1%, stability result is good.
4. comparison different in flow rate
B1401001 batches of Amino Acid Compound Injection (18AA) samples are taken, other chromatographic conditions are constant, set flow velocity respectively
Sample introduction when 1.0ml/min, 1.2ml/min and 1.4ml/min, records chromatogram.Result of the test is shown in Table 8：
Table 8 investigates the result of the test that the related material of tryptophan different in flow rate influences
The result shows that：Amino Acid Compound Injection (18AA) the condition it is different in flow rate under, the related material of tryptophan
For absolute value within ± 0.1%, stability result is good.
(8) solution stability testing
B1401001 batch Amino Acid Compound Injections (18AA) are taken, according in relation to the detection method under material item, respectively at 0,
2nd, each measure once, calculates the relative standard deviation of its impurity peak area, the result is shown in table 9 below when 4,6,8 is small.
The related material stability of 9 Amino Acid Compound Injection of table (18AA) tryptophan investigates result of the test
The result shows that：The related material of tryptophan measures in 8h in Amino Acid Compound Injection (18AA), and tryptophan is related
For the absolute value of material within ± 0.1%, stability of solution result is good.
(9) methodology validation result is as shown in table 10 below.
10 methodology validation result summary sheet of table
4th, sample measures
(1) the related substance-measuring method of tryptophan is shone, measures Amino Acid Compound Injection (18AA) reference preparation and trial production
Content of the tryptophan in relation to material in continuous 3 batches of Amino Acid Compound Injections (18AA) sample, the results are shown in Table 11.
The related content of material measurement result of 11 Amino Acid Compound Injection of table (18AA) tryptophan
The result shows that：The related material peak area of the tryptophan of reference preparation and 3 batches of samples is no more than acetyltryptophan pair
According to 5 times (1.0%) of product peak area, as a result well.
(2) the related substance-measuring method of tryptophan is shone, measures the stability Amino Acid Compound Injection of 24 months respectively
(18AA), Amino Acid Compound Injection (18AA-II) and amino acid (15) double peptides (2) parenteral solution, the result is shown in table 12 below, its
Middle Amino Acid Compound Injection (18AA), Amino Acid Compound Injection (18AA-II) and amino acid (15) double peptides (2) injection
The chromatogram of liquid refers to Figure 18, Figure 19, Figure 20 respectively.
The related substance-measuring result of 12 different aminoacids class parenteral solution tryptophan of table
The result shows that：Amino Acid Compound Injection (18AA), Amino Acid Compound Injection (18AA-II), 15% compound ammonia
Base acid injection (17AA), the related material peak area of tryptophan of amino acid (15) double peptides (2) parenteral solution are no more than second
5 times (1.0%) of acyl tryptophan product peak area, as a result well.
The method of the present invention is described by preferred embodiment, and related personnel substantially can be in present invention, essence
To method described herein and apply in god and scope and is modified or suitably changes with combining, to realize and using skill of the present invention
Art.In particular, all similar substitutions and modifications are apparent to those skilled in the art, they
It is considered as being included in the present invention.
Claims (4)
1. a kind of measure assay method of the amino acids parenteral solution tryptophan in relation to material, it is characterized in that, using high-efficient liquid phase color
Spectrometry, with the chromatographic column that octadecylsilane chemically bonded silica is stationary phase, gradient elution is carried out by following mobile phase condition；Including
Three kinds of mobile phases, mobile phase A are 0.01mol/L sodium dihydrogen phosphates, and PH=7.2 is adjusted with sodium hydroxide solution；Mobile phase B is second
Nitrile, methanol, water are according to volume ratio 45:45:10 mixing gained；Mobile phase C is methanol, water is according to 10:90 volume ratio mixing institute
；The gradient of mobile phase sets as follows：
2. a kind of measure assay method of the amino acids parenteral solution tryptophan in relation to material according to claim 1, it is special
Sign is, selects acetyltryptophan as own control.
3. a kind of measure assay method of the amino acids parenteral solution tryptophan in relation to material according to claim 2, it is special
Sign is, according to gained collection of illustrative plates, the peak after 0.54 times of tryptophan relative retention time, removes tryptophan relative retention time
It is the related material peak of tryptophan outside 0.78 times of peak and tryptophan peak.
A kind of 4. measure of the measure amino acids parenteral solution tryptophan in relation to material according to claim 1-3 any one
Method, it is characterised in that the column temperature is 40 DEG C, Detection wavelength 220nm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711050017.8A CN107907603B (en) | 2017-10-31 | 2017-10-31 | Method for measuring tryptophan related substances in amino acid injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711050017.8A CN107907603B (en) | 2017-10-31 | 2017-10-31 | Method for measuring tryptophan related substances in amino acid injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107907603A true CN107907603A (en) | 2018-04-13 |
| CN107907603B CN107907603B (en) | 2021-01-05 |
Family
ID=61842227
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711050017.8A Active CN107907603B (en) | 2017-10-31 | 2017-10-31 | Method for measuring tryptophan related substances in amino acid injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107907603B (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108663448A (en) * | 2018-05-14 | 2018-10-16 | 中国医学科学院医药生物技术研究所 | Detection method in relation to substance in a kind of Amino Acid Compound Injection |
| CN109406684A (en) * | 2018-12-26 | 2019-03-01 | 北京哈三联科技有限责任公司 | A kind of detection method measuring impurity B in the Amino Acid Compound Injection containing tryptophan, C, D content |
| CN112578031A (en) * | 2019-09-30 | 2021-03-30 | 天津药业研究院股份有限公司 | Method for detecting tryptophan impurities and application |
| CN112595802A (en) * | 2020-12-31 | 2021-04-02 | 辰欣药业股份有限公司 | Method for detecting content of compound amino acid injection for children |
| CN112858556A (en) * | 2021-01-14 | 2021-05-28 | 费森尤斯卡比华瑞制药有限公司 | Method for detecting tryptophan impurities in compound amino acid solution |
| CN112924566A (en) * | 2019-12-05 | 2021-06-08 | 湖北远大生物技术有限公司 | Method for simultaneously detecting glycine and serine in enzymatic reaction liquid |
| CN112946099A (en) * | 2021-01-25 | 2021-06-11 | 石家庄四药有限公司 | Method for detecting related substances in amino acid glucose injection |
| WO2022049213A1 (en) | 2020-09-02 | 2022-03-10 | Immundiagnostik Ag | Test kit and method of determining tryptophan in extracts of faecal samples |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1053128A (en) * | 1990-01-04 | 1991-07-17 | 宜昌市药品检验所 | The high-efficient liquid phase chromatogram process measuring method of 18 compound amino-acids injection liq |
| CN102440989A (en) * | 2010-10-13 | 2012-05-09 | 四川科伦药物研究有限公司 | Compound amino acid injection and preparation method and detection method thereof |
| CN103134892A (en) * | 2011-11-30 | 2013-06-05 | 天津金耀集团有限公司 | Analytical method of compound amino acid (15) double peptide (2) injection |
| CN104391053A (en) * | 2014-10-30 | 2015-03-04 | 广东新峰药业股份有限公司 | PR-HPLC (phase reversing-high performance liquid chromatography) determination method for simultaneously determining contents of five amino acids in earthworm injection |
| CN106950306A (en) * | 2017-03-28 | 2017-07-14 | 武汉半天科技开发有限公司 | A kind of method of cysteine content in measure Amino Acid Compound Injection |
-
2017
- 2017-10-31 CN CN201711050017.8A patent/CN107907603B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1053128A (en) * | 1990-01-04 | 1991-07-17 | 宜昌市药品检验所 | The high-efficient liquid phase chromatogram process measuring method of 18 compound amino-acids injection liq |
| CN102440989A (en) * | 2010-10-13 | 2012-05-09 | 四川科伦药物研究有限公司 | Compound amino acid injection and preparation method and detection method thereof |
| CN103134892A (en) * | 2011-11-30 | 2013-06-05 | 天津金耀集团有限公司 | Analytical method of compound amino acid (15) double peptide (2) injection |
| CN104391053A (en) * | 2014-10-30 | 2015-03-04 | 广东新峰药业股份有限公司 | PR-HPLC (phase reversing-high performance liquid chromatography) determination method for simultaneously determining contents of five amino acids in earthworm injection |
| CN106950306A (en) * | 2017-03-28 | 2017-07-14 | 武汉半天科技开发有限公司 | A kind of method of cysteine content in measure Amino Acid Compound Injection |
Non-Patent Citations (7)
| Title |
|---|
| ALMUTHESSE等: "Protein Quantification by Derivatization-Free High-Performance Liquid Chromatography of Aromatic Amino Acids", 《JOURNAL OF AMINO ACIDS》 * |
| P. NIKITAS等: "Multilinear gradient elution optimization in reversed-phase liquid chromatography using genetical gorithms", 《JOURNAL OF CHROMATOGRAPHY A》 * |
| PANAGIOTA AGRAFIOTOU等: "Direct RP-HPLC determination of underivatized amino acids with online dual UV absorbance, fluorescence, and multiple electrochemical detection", 《J. SEP. SCI.》 * |
| 方加林等: "复方氨基酸注射液中氨基酸含量快速分离测定法", 《安徽医药》 * |
| 王菲菲等: "高效薄层色谱、柱前衍生−超高效液相色谱和离子色谱分析疏血通注射液中游离氨基酸的比较", 《药学学报》 * |
| 陆柳容等: "国产色谱柱在复方氨基酸输液含量测定中的应用研究", 《氨基酸和生物资源》 * |
| 高春等: "18种复合氨基酸注射液中乙酰- L-酪氨酸及 L-色氨酸含量测定方法的研究", 《中国生化药物杂志》 * |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108663448A (en) * | 2018-05-14 | 2018-10-16 | 中国医学科学院医药生物技术研究所 | Detection method in relation to substance in a kind of Amino Acid Compound Injection |
| CN108663448B (en) * | 2018-05-14 | 2021-07-13 | 中国医学科学院医药生物技术研究所 | Method for detecting related substances in compound amino acid injection |
| CN109406684A (en) * | 2018-12-26 | 2019-03-01 | 北京哈三联科技有限责任公司 | A kind of detection method measuring impurity B in the Amino Acid Compound Injection containing tryptophan, C, D content |
| CN109406684B (en) * | 2018-12-26 | 2021-11-12 | 北京哈三联科技有限责任公司 | Detection method for determining content of impurity B, C, D in tryptophan |
| CN112578031A (en) * | 2019-09-30 | 2021-03-30 | 天津药业研究院股份有限公司 | Method for detecting tryptophan impurities and application |
| CN112924566A (en) * | 2019-12-05 | 2021-06-08 | 湖北远大生物技术有限公司 | Method for simultaneously detecting glycine and serine in enzymatic reaction liquid |
| CN112924566B (en) * | 2019-12-05 | 2023-12-26 | 湖北远大生物技术有限公司 | Method for simultaneously detecting glycine and serine in enzymatic reaction liquid |
| WO2022049213A1 (en) | 2020-09-02 | 2022-03-10 | Immundiagnostik Ag | Test kit and method of determining tryptophan in extracts of faecal samples |
| CN112595802A (en) * | 2020-12-31 | 2021-04-02 | 辰欣药业股份有限公司 | Method for detecting content of compound amino acid injection for children |
| CN112858556A (en) * | 2021-01-14 | 2021-05-28 | 费森尤斯卡比华瑞制药有限公司 | Method for detecting tryptophan impurities in compound amino acid solution |
| CN112946099A (en) * | 2021-01-25 | 2021-06-11 | 石家庄四药有限公司 | Method for detecting related substances in amino acid glucose injection |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107907603B (en) | 2021-01-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107907603A (en) | A kind of measure assay method of the amino acids parenteral solution tryptophan in relation to material | |
| CN112946099B (en) | Method for detecting related substances in amino acid glucose injection | |
| CN105092741B (en) | Method for detecting 3-amino-2-caprolactam through high performance liquid chromatography | |
| CN102749397A (en) | Analysis method of compound amino acid and dipeptide injection | |
| CN108663448A (en) | Detection method in relation to substance in a kind of Amino Acid Compound Injection | |
| CN106841408B (en) | The rapid detection method of methionine sulfoxide in a kind of amino acid injection | |
| Shim et al. | Method validation of 16 types of structural amino acids using an automated amino acid analyzer | |
| CN104280475A (en) | Method for detecting content of amino acid and glycyl glutamine in compound amino acid (15) dipeptide (2) injection | |
| CN102305831B (en) | Method for detecting cerebroprotein hydrolysate tablets | |
| CN105223280A (en) | A kind of black-bone chicken increases the assay method of amino acid content in emulsion formulation | |
| CN108459105B (en) | Method for simultaneously determining five preservatives in leather by adopting ultra-high performance synthetic phase chromatography | |
| CN104569238A (en) | Method for measuring content of amino acid in amino acid chromium complex | |
| WO2021179535A1 (en) | Method for determining content of compound amino acid injection | |
| CN108828085A (en) | A kind of total amino acid quantitative detecting method of transfer factor capsule | |
| CN105424834B (en) | Detect 2-Pyrrolidone and formic acid method in PVP K30 simultaneously | |
| CN113514589B (en) | High performance liquid chromatography analysis method of stannous glucoheptonate relative substance for injection | |
| CN109239219A (en) | The quantitative detecting method of polypeptide in a kind of transfer factor capsule | |
| CN108333267A (en) | The method for measuring arginine content in the multiple pleasure of inscription using high performance liquid chromatography | |
| CN114563495A (en) | Detection method of acetylcysteine and related substances thereof | |
| CN113390999A (en) | Control and detection method for sodium nitroprusside degradation impurities | |
| CN103512965A (en) | Detection method for impurities in amikacin sulfate injection | |
| Li et al. | Direct and simultaneous determination of methionine sulfoxide and pyroglutamic acid impurities in Compound Amino Acid Injection‐18 AA by ion‐pair reversed‐phase HPLC | |
| Swanepoel et al. | Fluorimetric method of analysis for D-norpseudoephedrine hydrochloride, glycine and L-glutamic acid by reversed-phase high-performance liquid chromatography | |
| CN106706787B (en) | The detection method and application of lysine content in a kind of aspirin-Al-lysine for injection | |
| CN112305138B (en) | Method for simultaneously determining content of lysine and glycine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20211231 Address after: 432000 No. 25, Xiaohan Avenue, high tech Zone, Xiaogan City, Hubei Province Patentee after: HUBEI HUAREN TONGJI PHARMACEUTICAL CO.,LTD. Address before: 266101 No. 187 Zhuzhou Road, Laoshan District, Qingdao, Shandong. Patentee before: HUAREN PHARMACEUTICAL Co.,Ltd. |
|
| TR01 | Transfer of patent right |