CN109239208A - A kind of quality determining method of Syprine Hydrochloride - Google Patents
A kind of quality determining method of Syprine Hydrochloride Download PDFInfo
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- G—PHYSICS
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Abstract
The present invention provides a kind of quality determining methods of Syprine Hydrochloride, it is impurity ethylenediamine, the diethylenetriamine, aminoethyl piperazine, three (2- amino-ethyl) amine, N- [2- (1- piperazinyl) ethyl] -1,2- ethylenediamine detected in Syprine Hydrochloride by gas chromatography.Detection method can detect ethylenediamine with quantitative analysis, diethylenetriamine, aminoethyl piperazine and three (2- amino-ethyl) amine, N- [2- (1- piperazinyl) ethyl] -1, the known impurities such as 2- ethylenediamine, specificity is strong, high sensitivity, favorable reproducibility, the related substance of Syprine Hydrochloride can be measured, it can be to 0.05% below three kind of known impurities diethylenetriamine of content, aminoethyl piperazine, three (2- amino-ethyl) amine are quantitative determined, and detection and separating capacity of the increase to other unknown impurities, it is high and the technology prejudice of vapor detection can not be carried out to overcome Syprine Hydrochloride boiling point.Syprine Hydrochloride quality determining method of the present invention is easy to operate, can effectively save analysis time, improves working efficiency.
Description
Technical field
The present invention relates to a kind of quality determining methods of Syprine Hydrochloride.Belong to drug tests.
Background technique
Hepatolenticular degeneration is also known as hepatolenticular degeneration, belongs to a kind of copper dysbolism disease of autosomal recessive inheritance, is
As caused by the ATP7B gene mutation of patient.Clinically, which has liver type, brain type, mixed type and asymptomatic, main
Show as the symptom of psychoneural and liver etc., specially extrapyramidal symptoms, the cirrhosis, essence of progressive exacerbation
Refreshing symptom, kidney function damage and Kayser-Fleischer ring.
The illness rate of hepatolenticular degeneration worldwide is 3/,100,000 people, and wherein gene carrier accounts for 1/90.Such
The therapeutic scheme of illness follows the principle of early diagnosis and early treatment, still, before mutated gene fails thoroughly to correct, medicine
The purpose of object treatment can only be the excretion for promoting internal copper and the absorption for reducing copper, and this is the life for needing to maintain for a long time
Biochemical process is managed, therefore patient needs to receive lifelong drug therapy, including drives copper drug, prevents enteron aisle to Copper uptakie and rush
Into the drug and symptomatic treatment of row's copper.
Currently, the drug for the treatment of hepatolenticular degeneration is mostly using penicillamine, but the clinical data table of many years
Bright, 25%~30% may occur in which various adverse reactions in the patient for receiving penicillamine treatment, such as: fash, the acute mistake of fever
Quick reaction；The reaction of the subacute toxicities such as bone marrow suppression, albuminuria；And the slow poisoning of collagen and immune system may be influenced
Reaction, such as wrinkle of skin, abdomen scar are formed, boring shape elastosis skin lesion of crawling, empsyxis, ephritis
The more serious disease of immune system such as syndrome, systemic loupus erythematosus and myasthenia gravis, and therefore can occur being discontinued, subtract
Measure or glucocorticoid need to be taken etc..More seriously, nervous system type patient using penicillamine carry out initial treatment, about 20%~
50% patient's early stage occurs brain symptom and deteriorates, though wherein the neurosis that about 25% patient through active treatment, has deteriorated
Shape cannot still be restored to the level before treatment, therefore many patients cause serious deformity.Therefore, most of America and Europes in recent years
Neurological Clinics doctor does not recommend initial treatment drug of the penicillamine as nervous system type patient.
Syprine Hydrochloride mechanism of action is similar to penicillamine, and copper is mobilized from tissue, works fast compared with penicillamine.This
Outside, Syprine Hydrochloride can also prevent and stop the rapid clinical deterioration rates after penicillamine treatment, therefore, can be used for producing penicillamine
The patient of raw serious toxicity reaction.It is at present choice drug in the treatment of liver type patient, can additionally combine with zinc preparation makes
With.For penicillamine earlier, the side effect of Syprine Hydrochloride is seldom, and also there is no the allergic reaction about the medicine
Report.
The entitled triethylene tetramine dihydrochloride of chemistry of Syprine Hydrochloride, structure are as follows:
Yuan Yan company is Merck, trade name Syprine, molecular formula C6H18N42HCl, relative molecular mass
It is 219.16, fusing point is 115 DEG C~118 DEG C.
In order to preferably control the quality of Syprine Hydrochloride, guarantees the drug safety and validity of Syprine Hydrochloride, have
Necessity is established the strong analyzing detecting method of high sensitivity, specificity and is fully and effectively controlled to its technique and degradation impurity
System, including specific known impurities and other potential impurity.
In existing USP standard, limit test has been carried out using related substance of the thin-layered chromatography to Syprine Hydrochloride, has been wrapped
Three kinds of known impurities such as diethylenetriamine, aminoethyl piperazine, three (2- amino-ethyl) amine are included, Control of Impurities limit is total miscellaneous
Matter only 2.0%, does not provide the limit of single impurity.It is found through experiment that diethylenetriamine, aminoethyl piperazine, three (2- amino
Ethyl) when content is lower (respectively below 0.5%), the thin-layered chromatography in USP just cannot effectively examine it amine
Out, the poor sensitivity of this method；Other unknown impurities in Syprine Hydrochloride are also failed to effectively detect.Therefore, USP mass
Thin-layered chromatography is unable to reach effectively control purpose of this product in relation to substance in standard, therefore does not use this method to measure this product to have
Close substance.
On the basis of USP standard, document (Journal of Chromatographic Science, Vol.45,
July 2007, P315-318) thin-layered chromatography is improved, photo densitometry is used, to four hydrochloride of trientine
Above three impurity quantitative determined.But this method still has larger defect, one side this method is only capable of to upper
Three specific impurities stated are separated, and other impurity that may be present cannot be analyzed and this method it is fatal
Defect；On the other hand, although the sensitivity of this method makes moderate progress, the detection limit of diethylenetriamine is still up to
27.5ng, and its is complicated for operation, time-consuming and laborious, has particular/special requirement to detection device, the application being unsuitable in pharmaceuticals industry pushes away
Extensively.
Summary of the invention
The technical solution of the present invention is to provide a kind of quality determining methods of Syprine Hydrochloride.
The present invention provides a kind of quality determining methods of Syprine Hydrochloride, it is to detect hydrochloric acid by gas chromatography
Impurity ethylenediamine, diethylenetriamine, aminoethyl piperazine, three (2- amino-ethyl) amine, N- [2- (1- piperazinyl) in trientine
Ethyl] -1,2- ethylenediamine.
Quality determining method of the present invention includes the following steps:
A, sample pre-treatments: taking Syprine Hydrochloride sample, and aqueous slkali is added, and adds dilution dilution agent that sample solution is made；
B, it is detected using gas chromatography, chromatographic condition are as follows:
Chromatographic column is low pole quartz capillary column or the quartz capillary column for being applicable in amine；The gas chromatography
Column temperature temperature program is as follows: 50 DEG C~220 DEG C of initial temperature, maintaining 5~50 minutes, then with the heating of 0~20 DEG C/min rate
To 190~250 DEG C, 5~20min is maintained；
The conditional parameter of the gas chromatography are as follows: injector temperature is 220~300 DEG C, using hydrogen flameionization
Detector (FID), detector temperature are 250~350 DEG C；Carrier gas is nitrogen or helium, and flow velocity is 1~5mL/min, split ratio
For 5:1~50:1；The sample volume of sample is 0.1 μ of μ L~50 L；
Wherein, sample-pretreating method described in a step are as follows: take Syprine Hydrochloride sample, aqueous slkali is added, adds water dilute
It releases constant volume and sample solution is made, sample concentration is 5mg/mL~100mg/mL.
Wherein, the alkali soluble liquid alkaline includes the alkaline water made of sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonium hydroxide
Solution.
Wherein, the concentration of the aqueous slkali is 0.5~10mol/L.
Wherein, pH >=10 of the sample solution.
It is further preferred that the column temperature temperature program of the gas chromatography is as follows: 50 DEG C~200 DEG C of initial temperature,
It maintains 5~50 minutes, is then warming up to 190~230 DEG C with 0~10 DEG C/min rate, maintain 5~20min.
It is further preferred that the conditional parameter of the gas chromatography are as follows: injector temperature is 250~300 DEG C, is adopted
With flame ionization ditector (FID), detector temperature is 250~300 DEG C；Carrier gas is nitrogen, and flow velocity is 1~5mL/
Min, split ratio are 5:1~20:1；The sample volume of sample is 0.5 μ of μ L~20 L.
The detection technique reported at present is tested using thin layer, be according to the property of Syprine Hydrochloride itself (no
Change its property) inspection that carries out, by reducing, the boiling point of Syprine Hydrochloride, to be adapted to gas phase condition be difficult to realize.
Detection method can detect ethylenediamine, diethylenetriamine, aminoethyl piperazine and three (2- ammonia with quantitative analysis
Base ethyl) known impurities such as amine, N- [2- (1- piperazinyl) ethyl] -1,2- ethylenediamine, specificity is strong, high sensitivity, reproducibility
It is good, the related substance of Syprine Hydrochloride can be measured, can three kinds of known impurities of content 0.05% be carried out with quantitative survey
It is fixed, and increase the detection and separating capacity to other unknown impurities, it overcomes Syprine Hydrochloride boiling point height and gas phase can not be carried out
The technology prejudice of detection.Syprine Hydrochloride quality determining method of the present invention is easy to operate, can effectively save analysis time, mention
High working efficiency.
Obviously, above content according to the present invention is not taking off according to the ordinary technical knowledge and customary means of this field
Under the premise of the above-mentioned basic fundamental thought of the present invention, the modification, replacement or change of other diversified forms can also be made.
The specific embodiment of form by the following examples remakes above content of the invention further detailed
Explanation.But the range that this should not be interpreted as to the above-mentioned theme of the present invention is only limitted to example below.It is all above-mentioned interior based on the present invention
Hold realized technology to all belong to the scope of the present invention.
Detailed description of the invention
Fig. 1 is the map that 6 samples obtain in test example 3；
Fig. 2 is the map that processing mode 1 obtains in test example 4；
Fig. 3 is the map that processing mode 2 obtains in test example 4.
Specific embodiment
The quality determining method of the Syprine Hydrochloride of the present invention of embodiment 1
Using Agilent 7890A gas chromatograph.
This product about 50mg is taken, it is accurately weighed, add 0.3mL 3mol/L ammonia spirit, adds water to be quantitatively diluted to 10mL, shake
It is even, as sample solution；Another precision weighs impurity ethylenediamine, diethylenetriamine, aminoethyl piperazine and three (2- amino-ethyls)
Amine, N- [2- (1- piperazinyl) ethyl] -1,2- ethylenediamine reference substance are each appropriate, and being dissolved in water and quantifying dilution is made in every 1mL
Mixed solution containing each 50 μ g of impurity positions solution as impurity；With CP-Volamine (0.53mm × 30m × 0.5 μm) quartz
Capillary column is chromatographic column, and 190 DEG C maintain 40 minutes；Column flow rate is 1.0mL/min；Detector is hydrogen flameionization detection
Device (FID), detector temperature are 350 DEG C；Injector temperature is 300 DEG C, split ratio 5:1.Precision measures impurity and positions solution
And each 0.1 μ L of test solution, it is injected separately into gas chromatograph, chromatogram is recorded, according to area normalization method calculated result.
Measurement result:
The quality determining method of the Syprine Hydrochloride of the present invention of embodiment 2
Using Agilent 7890A gas chromatograph.
This product about 100mg is taken, it is accurately weighed, add 1.5mL 1mol/L ammonia spirit, adds water to be quantitatively diluted to 10mL, shake
It is even, as sample solution；Another precision weighs impurity ethylenediamine, diethylenetriamine, aminoethyl piperazine and three (2- amino-ethyls)
Amine, N- [2- (1- piperazinyl) ethyl] -1,2- ethylenediamine reference substance are each appropriate, and being dissolved in water and quantifying dilution is made in every 1mL
Mixed solution containing each 30 μ g of impurity positions solution as impurity；With CP-Volamine (0.32mm × 30m × 3 μm) quartz wool
Capillary column is chromatographic column, 50 DEG C of initial temperature, maintains 5min, is then warming up to 200 DEG C with 20 DEG C/min rate, maintains
20min；Column flow rate is 1.5mL/min；Detector is flame ionization ditector (FID), and detector temperature is 320 DEG C；Into
Sample mouth temperature is 280 DEG C, split ratio 10:1.Precision measures impurity positioning solution and each 0.5 μ L of test solution, infuses respectively
Enter gas chromatograph, chromatogram is recorded, according to area normalization method calculated result.
Measurement result:
The quality determining method of the Syprine Hydrochloride of the present invention of embodiment 3
Using Agilent 7890A gas chromatograph.
This product about 200mg is taken, it is accurately weighed, add 0.5mL 10mol/L potassium hydroxide solution, adds water-ethanol (70:30)
It is quantitatively diluted to 10mL, is shaken up, as sample solution；Another precision weighs impurity ethylenediamine, diethylenetriamine, aminoethyl piperazine
And three (2- amino-ethyl) amine, N- [2- (1- piperazinyl) ethyl] -1,2- ethylenediamine reference substance are each appropriate, add water-ethanol (70:
30) it dissolves and quantifies the mixed solution that dilution is made containing each 20 μ g of impurity in every 1mL and position solution as impurity；With CP-
Volamine (0.32mm × 30m × 3 μm) quartz capillary column is chromatographic column, 100 DEG C of initial temperature, maintains 20min, then
220 DEG C are warming up to 10 DEG C/min rate, maintains 10min；Column flow rate is 2.0mL/min；Detector is hydrogen flameionization inspection
It surveys device (FID), detector temperature is 300 DEG C；Injector temperature is 260 DEG C, split ratio 20:1.Precision measures impurity positioning
Solution and each 1.0 μ L of test solution are injected separately into gas chromatograph, record chromatogram, calculate and tie according to area normalization method
Fruit.
Measurement result:
The quality determining method of the Syprine Hydrochloride of the present invention of embodiment 4
Using Agilent 7890A gas chromatograph.
This product about 150mg is taken, it is accurately weighed, add 4mL 0.5mol/L sodium bicarbonate solution, adds water-methanol (50:50) fixed
Amount is diluted to 5mL, shakes up, as sample solution；Another precision weighs impurity ethylenediamine, diethylenetriamine, aminoethyl piperazine and three
(2- amino-ethyl) amine, N- [2- (1- piperazinyl) ethyl] -1,2- ethylenediamine reference substance are each appropriate, add water-methanol (50:50)
It dissolves and quantifies the mixed solution that dilution is made containing each 10 μ g of impurity in every 1mL and position solution as impurity；With CP-
Volamine (0.32mm × 30m × 3 μm) quartz capillary column is chromatographic column, 220 DEG C of initial temperature, maintains 50min, then
250 DEG C are warming up to 4 DEG C/min rate, maintains 5min；Column flow rate is 2.5mL/min；Detector is hydrogen flameionization inspection
It surveys device (FID), detector temperature is 270 DEG C；Injector temperature is 250 DEG C, split ratio 30:1.Precision measures impurity positioning
Solution and each 20 μ L of test solution are injected separately into gas chromatograph, record chromatogram, calculate and tie according to area normalization method
Fruit.
The quality determining method of the Syprine Hydrochloride of the present invention of embodiment 5
Using Agilent 7890A gas chromatograph.
This product about 400mg is taken, it is accurately weighed, add 1mL 5mol/L sodium bicarbonate solution, adds water-ethanol (20:80) quantitative
It is diluted to 10mL, is shaken up, as sample solution；Another precision weighs impurity ethylenediamine, diethylenetriamine, aminoethyl piperazine and three
(2- amino-ethyl) amine, N- [2- (1- piperazinyl) ethyl] -1,2- ethylenediamine reference substance are each appropriate, add water-ethanol (20:80)
It dissolves and quantifies the mixed solution that dilution is made containing each 50 μ g of impurity in every 1mL and position solution as impurity；With HP-5
(0.53mm × 30m × 2 μm) quartz capillary column is chromatographic column, 200 DEG C of initial temperature, 25min is maintained, then with 2 DEG C/min
Rate is warming up to 230 DEG C, maintains 15min；Column flow rate is 4mL/min；Detector is flame ionization ditector (FID), inspection
Surveying device temperature is 250 DEG C；Injector temperature is 220 DEG C, split ratio 40:1.Precision measures impurity positioning solution and test sample
Each 30 μ L of solution is injected separately into gas chromatograph, chromatogram is recorded, according to area normalization method calculated result.
The quality determining method of the Syprine Hydrochloride of the present invention of embodiment 6
Using Agilent 7890A gas chromatograph.
This product about 500mg is taken, it is accurately weighed, add 4mL 2mol/L solution of potassium carbonate, adds water to be quantitatively diluted to 5mL, shake
It is even, as sample solution；Another precision weighs impurity ethylenediamine, diethylenetriamine, aminoethyl piperazine and three (2- amino-ethyls)
Amine, N- [2- (1- piperazinyl) ethyl] -1,2- ethylenediamine reference substance are each appropriate, and being dissolved in water and quantifying dilution is made in every 1mL
Mixed solution containing each 30 μ g of impurity positions solution as impurity；With DB-1 (0.32mm × 20m × 30 μm) quartz capillary column
For chromatographic column, 220 DEG C are maintained 35 minutes；Column flow rate is 5mL/min；Detector is flame ionization ditector (FID), inspection
Surveying device temperature is 300 DEG C；Injector temperature is 290 DEG C, split ratio 50:1.Precision measures impurity positioning solution and test sample
Each 50 μ L of solution is injected separately into gas chromatograph, chromatogram is recorded, according to area normalization method calculated result.
Beneficial effects of the present invention are proved below by way of actual conditions screening test.
The detection of experimental example 1 limit and quantitative limit
Ethylenediamine, diethylenetriamine, aminoethyl piperazine and three (2- amino-ethyl) amine, N- [2- (1- piperazinyl) are taken respectively
Ethyl] solution that signal-to-noise ratio is about 10:1 is made in -1,2- ethylenediamine reference substance, as quantitative limit comparison liquid；Signal-to-noise ratio, which is made, is
The solution of 3:1 limits comparison liquid as detection, measures respectively by the chromatographic condition sample introduction of 1~embodiment of embodiment 6, records chromatography
Figure.It is as follows to measure result:
As can be seen from the results, this method is good for detecting sensitivity of the Syprine Hydrochloride in relation to substance, can reach effective control
Purpose of this product in relation to substance.
The test of 2 sample recovery rate of experimental example
To ethylenediamine, diethylenetriamine, aminoethyl piperazine, three (2- amino-ethyl) amine, N- [2- (1- piperazinyl) second
Base] be separately added into the sample that determines of the known impurity levels such as -1,2- ethylenediamine 0.16%, 0.20%, 0.24% it is each known
Impurity, each weight respectively take 3 parts, set in 10mL measuring bottle, prepare solution with condition as described in Example 5 and measure.Measurement knot
Fruit is as follows:
According to the experimental results, under the gas phase process, the average recovery rate of each known impurities of Syprine Hydrochloride is
98.63%~100.11%, RSD are respectively less than 1.00%, and the accuracy of the above-mentioned each impurity of illustration method quantitative detection is good.
3 repetitive test of experimental example
6 parts of samples are made according to the method for embodiment 5 in Syprine Hydrochloride, number is respectively 1,2,3,4,5,6, to upper
It states 6 parts of samples to be tested respectively under conditions of embodiment 5, is detailed in Fig. 1, test result is as follows.
It can be seen that the test result of the method for the present invention is reproducible, as a result reliably.
Shadow of the sample solution pH difference to testing result in the quality determining method of the Syprine Hydrochloride of the present invention of experimental example 4
It rings
Specific experiment method and result are as follows:
1, the selection of sample handling characteristics
This product is the dihydrochloride of trientine alkali, and boiling point is much higher than trientine alkali, therefore can not be under GC conditions
Appearance, in relation to needing to measure after alkali process is translated into trientine alkali using gas chromatography when substance-measuring.
Chromatographic condition uses condition 1:
Chromatographic column: Agilent CP-Volamine capillary chromatographic column (0.32mm × 30m)
Column temperature: 80 DEG C of initial column temperature, 220 DEG C is risen to the heating rate of 5 DEG C/min, maintains 25min；
Carrier gas (N2) flow velocity: 2mL/min；(constant current mode)
Air velocity: 300mL/min；Hydrogen flow rate: 30mL/min；
Injector temperature: 250 DEG C；
Detector (FID) temperature: 350 DEG C；
1 μ l of sample volume；Split ratio: 40:1；
Take Syprine Hydrochloride sample appropriate, it is accurately weighed, it is separately added into different amounts of 1mol/L NaOH solution and ammonium hydroxide
It is diluted with water after progress basification and the solution that concentration is about 30mg/mL is made, investigate the detection situation of main peak and impurity.
1 sample handling characteristics of table selection -1
The related material sample testing result that same batch Syprine Hydrochloride sample difference alkalization mode is handled see the table below andFig. 2 and Fig. 3.(Fig. 2 is the gas phase map of processing mode 1, and Fig. 3 is the map of processing mode 2)
The result shows that be added in Syprine Hydrochloride sample different amounts of 1mol/L NaOH its in relation to substance-measuring result
In apparent regularity.When NaOH additional amount be 1mL when, the pH of sample solution is about 9, principal component due toFail to convert completely To trientine alkali, thereforeIt can not normal appearance, cause chromatographic peak in test map more and miscellaneous；Increase with NaOH dosage, sample is complete
Full alkalization, can normal appearance；When NaOH additional amount increases to 2mL and 2mL or more, sample main peak area and the detection of each impurity
Amount reaches unanimity, that is, illustrates the 1mol/L NaOH that 2mL is added, when the pH >=10 of sample solution, sample can be made sufficiently to convert
For trientine alkali；Concentrated ammonia liquor processing sample detection is added as a result, its impurity detection type and data are handled with NaOH in another compare
Sample it is consistent, ammonium hydroxide not appearance does not interfere the detection of impurity, can select ammonium hydroxide for the related substance-measuring sample of this product yet
Pre-treatment.
Claims (8)
1. a kind of quality determining method of Syprine Hydrochloride, it is characterised in that: it is to detect salt love song grace by gas chromatography
Impurity ethylenediamine, diethylenetriamine, aminoethyl piperazine, three (2- amino-ethyl) amine, N- [2- (1- piperazinyl) ethyl]-in spit of fland
1,2- ethylenediamine.
2. detection method according to claim 1, it is characterised in that: it includes the following steps:
A, sample pre-treatments: taking Syprine Hydrochloride sample, and aqueous slkali is added, and adds dilution dilution agent that sample solution is made；
B, it is detected using gas chromatography, chromatographic condition are as follows:
Chromatographic column is low pole quartz capillary column or the quartz capillary column for being applicable in amine；The column temperature liter of the gas chromatography
Warm program is as follows: 50 DEG C~220 DEG C of initial temperature, maintain 5~50 minutes, then 190 are warming up to 0~20 DEG C/min rate~
250 DEG C, maintain 5~20min；
The conditional parameter of the gas chromatography are as follows: injector temperature is 220~300 DEG C, is detected using hydrogen flameionization
Device (FID), detector temperature are 250~350 DEG C；Carrier gas is nitrogen or helium, and flow velocity is 1~5mL/min, split ratio 5:1
~50:1；The sample volume of sample is 0.1 μ of μ L~50 L.
3. detection method according to claim 2, it is characterised in that: sample-pretreating method described in a step are as follows: take salt
Aqueous slkali is added in sour trientine sample, is diluted with water constant volume and sample solution is made, sample concentration is 5mg/mL~100mg/mL.
4. detection method according to claim 3, it is characterised in that: the aqueous slkali includes by sodium hydroxide, hydrogen-oxygen
Change potassium, calcium hydroxide, alkaline aqueous solution made of ammonium hydroxide.
5. detection method according to claim 3 or 4, it is characterised in that: the concentration of the aqueous slkali be 0.5~
10mol/L。
6. detection method according to claim 3 or 4, which is characterized in that pH >=10 of the sample solution.
7. detection method according to claim 2, it is characterised in that: the column temperature temperature program of the gas chromatography is such as
Under: it 50 DEG C~200 DEG C of initial temperature, maintains 5~50 minutes, is then warming up to 190~230 DEG C with 0~10 DEG C/min rate, dimension
Hold 5~20min.
8. detection method according to claim 2, it is characterised in that: the conditional parameter of the gas chromatography are as follows: into
Sample mouth temperature is 250~300 DEG C, and using flame ionization ditector (FID), detector temperature is 250~300 DEG C；Carrier gas
For nitrogen, flow velocity is 1~5mL/min, and split ratio is 5:1~20:1；The sample volume of sample is 0.5 μ of μ L~20 L.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113484455A (en) * | 2021-07-27 | 2021-10-08 | 成都市海通药业有限公司 | Gas chromatography detection process of ethylenediamine |
| CN113514565A (en) * | 2020-04-10 | 2021-10-19 | 昆药集团股份有限公司 | Detection method of residual ethylenediamine and piperazine in homopiperazine |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4757144A (en) * | 1983-12-16 | 1988-07-12 | Kao Corporation | Preparing tertiary amine from formaldehyde and primary and/or secondary amine |
| CN1442402A (en) * | 2003-03-31 | 2003-09-17 | 大连理工大学 | Method of selectively synthesizing triethylene diamine |
| CN101704753A (en) * | 2009-11-17 | 2010-05-12 | 中国科学院大连化学物理研究所 | Method for preparing ethylene diamine from ethanolamine and ammonia serving as raw materials under hydrogen condition |
| CN105753719A (en) * | 2014-12-17 | 2016-07-13 | 四川科瑞德凯华制药有限公司 | Trientine hydrochloride compound |
-
2017
- 2017-07-11 CN CN201710561554.2A patent/CN109239208A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4757144A (en) * | 1983-12-16 | 1988-07-12 | Kao Corporation | Preparing tertiary amine from formaldehyde and primary and/or secondary amine |
| CN1442402A (en) * | 2003-03-31 | 2003-09-17 | 大连理工大学 | Method of selectively synthesizing triethylene diamine |
| CN101704753A (en) * | 2009-11-17 | 2010-05-12 | 中国科学院大连化学物理研究所 | Method for preparing ethylene diamine from ethanolamine and ammonia serving as raw materials under hydrogen condition |
| CN105753719A (en) * | 2014-12-17 | 2016-07-13 | 四川科瑞德凯华制药有限公司 | Trientine hydrochloride compound |
Non-Patent Citations (7)
| Title |
|---|
| A.A.CASSELMAN 等: "Gas chromatography of some polyamines on three porous polymer columns", 《JORMAL OF CHROMATOGRAPHY A》 * |
| IHOKO OGURA 等: "Characterization of Low-Molecular-Weight Polyethyleneimines Using GC/CI-MS and GC", 《ANALYTICAL SCIENCES》 * |
| THÉO HENRIET 等: "Solid state stability and solubility of triethylenetetramine dihydrochloride", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》 * |
| 孟袆 等: "N-β-羟乙基乙二胺在铜催化剂上的反应机理", 《化学研究与应用》 * |
| 徐伯洪 等: "《工作场所有害物质监测方法》", 31 May 2003, 中国人民公安大学出版社 * |
| 王丽华: "呱嗦及其共生物的气相色谱分析研究", 《理化检验-化学分册》 * |
| 邹栩 等: "《1984-1996世界上市新药》", 31 December 1996, 中国药科大学期刊编辑部 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113514565A (en) * | 2020-04-10 | 2021-10-19 | 昆药集团股份有限公司 | Detection method of residual ethylenediamine and piperazine in homopiperazine |
| CN113484455A (en) * | 2021-07-27 | 2021-10-08 | 成都市海通药业有限公司 | Gas chromatography detection process of ethylenediamine |
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