CN110174474A - The detection method of L MALIC ACID isomers in Multiple electrolytes injection (II) - Google Patents
The detection method of L MALIC ACID isomers in Multiple electrolytes injection (II) Download PDFInfo
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- CN110174474A CN110174474A CN201910441800.XA CN201910441800A CN110174474A CN 110174474 A CN110174474 A CN 110174474A CN 201910441800 A CN201910441800 A CN 201910441800A CN 110174474 A CN110174474 A CN 110174474A
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- malic acid
- multiple electrolytes
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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
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
- G01N30/12—Preparation by evaporation
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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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
- G01N30/14—Preparation by elimination of some components
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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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
- G01N30/12—Preparation by evaporation
- G01N2030/126—Preparation by evaporation evaporating sample
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Abstract
The present invention provides a kind of detection methods of L MALIC ACID isomers in Multiple electrolytes injection (II), the L MALIC ACID isomery body detecting method includes the following steps: to carry out pre-treatment to Multiple electrolytes injection (II) sample using hydrochloric acid and acetone, remove the interference of inorganic salts and water to L MALIC ACID in sample, then with forward direction chromatography determination L MALIC ACID content of isomer therein.
Description
Technical field
The invention belongs to L MALIC ACID isomeries in pharmaceutical technology field more particularly to a kind of Multiple electrolytes injection (II)
The detection method of body.
Background technique
Multiple electrolytes injection (II) be include sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium acetate and L- apple
The aqueous solution of tartaric acid.
Malic acid is the molecule containing chiral centre, and L MALIC ACID and D-malic acid are a pair of of isomers, have document to show L-
Malic acid has important physiological function, is the important intermediate of inside of human body circulation, is easily absorbed by the body, can be used for controlling
A variety of diseases such as hepatopathy, anaemia, hypoimmunity, uremia, hypertension, hepatic failure are treated, and anticancer drug can be mitigated to normal
The toxic action of cell.But D-malic acid is physiologically invalid.Therefore need to establish a kind of effective method, control compound electrolysis
The content of D-malic acid in matter injection (II), to guarantee the curative effect of Multiple electrolytes injection (II).
The section great thinkers of the past etc. are document " normal phase high performance liquid chromatography measures the enantiomter D-malic acid in L MALIC ACID "
In report measurement L MALIC ACID raw material in isomery body method.The method of use have certain specificity, be suitable for ingredient compared with
Isomers measures in single malic acid bulk pharmaceutical chemicals, and sample positive dilution is needed to dissolve before measurement, therefore is not suitable for ingredient
The direct detection of L MALIC ACID isomers in complicated Multiple electrolytes injection (II).
Du Xi etc. reports utilization in document " grape and the Derivative GC method of Organic Acids in Wine measurement "
Malonic acid, succinic acid, tartaric acid, malic acid, adipic acid, penta 2 in the derivative gas chromatographic detection grape wine of iodoethane and grape juice
The method of acid and citric acid.The derivative of sample needs to carry out addition reaction, Multiple electrolytes injection (II) before this method measures
In a large amount of inorganic salts for containing can interfere derivatization reaction, carry out derivatization reaction can not.
Domestic and foreign literature has no the detection method about L MALIC ACID isomers in Multiple electrolytes injection (II) at present
Report.The inorganic salts and water contained in Multiple electrolytes injection (II) can detect L MALIC ACID isomers and interfere, because
This needs to establish the content that new detection method effectively detects L MALIC ACID isomers in Multiple electrolytes injection (II), thus
Control the quality of Multiple electrolytes injection (II).
Summary of the invention
The purpose of the present invention is being directed to the blank of the prior art, L- apple in a kind of Multiple electrolytes injection (II) is provided
The detection method of acid isomer, solution avoid in Multiple electrolytes injection (II) inorganic salts and water to L MALIC ACID isomery physical examination
The problem of surveying interference, improves the sensitivity of detection method, specificity, and accuracy makes it meet the control of industrialized production quality
It is required that.
The detection method of L MALIC ACID isomers in Multiple electrolytes injection (II) of the present invention, specifically include as
Lower step:
(1) Multiple electrolytes injection (II) sample for taking 100ml adds appropriate concentrated hydrochloric acid to be uniformly mixed, and water bath method is cold
But to after room temperature plus water redissolves.Wherein 2ml is taken, is set in test tube, acetone is added, is vortexed 1 minute, filtering takes filtrate water bath method, cold
But to room temperature, add mobile phase ultrasound 2 minutes, filter to get test sample.
(2) hand that cellulose-three (3,5- dichlorophenyl carbamate) is stationary phase is covalently bonded with Silica Surface
Property chromatographic column, using n-hexane: isopropanol: dehydrated alcohol: trifluoroacetic acid is mobile phase, Detection wavelength 210nm, and 30 DEG C of column temperature.
In detection method, the Multiple electrolytes injection (II) is containing sodium chloride, potassium chloride, chlorination
Magnesium, calcium chloride, sodium acetate and L MALIC ACID aqueous solution.Its sampling amount is 100ml~500ml, preferably 200ml.
The pre-treatment is 2ml~5ml with concentrated hydrochloric acid dosage, preferably 2ml.
The dosage of redissolution water is 2ml~5ml, preferably 3ml.
Acetone dosage before the vortex is 3ml~10ml, preferably 3ml.
N-hexane ratio is 80%~95%, preferably 90% in the mobile phase;Isopropanol ratios are 0%~10%, excellent
Select 7%;Dehydrated alcohol ratio is 0%~10%, preferably 3%;Trifluoroacetic acid ratio is 0.1%.
The present invention uses enriching hydrochloric acid water bath method in Multiple electrolytes injection (II) sample pretreatment process, can be with
Remove the interference of sodium acetate;It is filtered after adding acetone to be vortexed, removes the interference of other inorganic salts and water, will be answered by two step pre-treatments
Inorganic salts and water thoroughly eliminate the detection of L MALIC ACID isomers in square electrolyte injection (II).
Sample detection process is covalently bonded with cellulose-three (3,5- dichlorophenyl carbamate) using Silica Surface
The chiral column of filler, the bonding filler are stablized with higher stability retention time compared to application type filler, can effectively be kept away
Exempt from interference of other impurity to its isomers in L MALIC ACID.
The present invention has the advantage that 1. have filled up the detection of L MALIC ACID isomers in Multiple electrolytes injection (II)
The blank of method.2. avoiding inorganic salts and water in Multiple electrolytes injection (II) to do L MALIC ACID isomers detection
It disturbs, while avoiding the interference of other impurities in detection using bonding filler chiral column, this method sensitivity, specificity, accurately
Degree is all satisfied the requirement that quality controls in industrialized production.
Detailed description of the invention
1 liquid chromatogram of Fig. 1 embodiment of the present invention
2 liquid chromatogram of Fig. 2 embodiment of the present invention
3 liquid chromatogram of Fig. 3 embodiment of the present invention
Fig. 41 liquid chromatogram of comparative example of the present invention
Specific embodiment
Embodiment below is that the present invention will be described in detail, is not intended to limit the present invention.
Embodiment 1
Detection method
(1) Multiple electrolytes injection (II) sample 200ml is taken, adds hydrochloric acid 2ml to be uniformly mixed, water bath method is cooled to
After room temperature plus water 3ml redissolves.Wherein 2ml is taken, is set in test tube, acetone 3ml is added, is vortexed 1 minute, filtering takes filtrate water bath method,
It is cooled to room temperature, adds mobile phase 3ml ultrasound 2 minutes, filter to get test sample.
(2) hand that cellulose-three (3,5- dichlorophenyl carbamate) is stationary phase is covalently bonded with Silica Surface
Property chromatographic column, using n-hexane: isopropanol: dehydrated alcohol: trifluoroacetic acid=90:7:3:0.1 is mobile phase, Detection wavelength 210nm,
30 DEG C of column temperature.
Embodiment 2
Detection method
(1) Multiple electrolytes injection (II) sample 300ml is taken, adds hydrochloric acid 5ml to be uniformly mixed, water bath method is cooled to
After room temperature plus water 2ml redissolves.Wherein 2ml is taken, is set in test tube, acetone 3ml is added, is vortexed 1 minute, filtering takes filtrate water bath method,
It is cooled to room temperature, adds mobile phase 3ml ultrasound 2 minutes, filter to get test sample.
(2) hand that cellulose-three (3,5- dichlorophenyl carbamate) is stationary phase is covalently bonded with Silica Surface
Property chromatographic column, using n-hexane: isopropanol: dehydrated alcohol: trifluoroacetic acid=95:5:0:0.1 is mobile phase, Detection wavelength 210nm,
30 DEG C of column temperature.
Embodiment 3
Detection method
(1) Multiple electrolytes injection (II) sample 500ml is taken, hydrochloric acid 3.5ml is added to be uniformly mixed, water bath method is cooling
After to room temperature plus water 5ml redissolves.Wherein 2ml is taken, is set in test tube, acetone 10ml is added, is vortexed 1 minute, filtering takes filtrate water-bath to steam
It is dry, it is cooled to room temperature, adds mobile phase 3ml ultrasound 2 minutes, filter to get test sample.
(2) hand that cellulose-three (3,5- dichlorophenyl carbamate) is stationary phase is covalently bonded with Silica Surface
Property chromatographic column, using n-hexane: isopropanol: dehydrated alcohol: trifluoroacetic acid=80:10:10:0.1 is mobile phase, Detection wavelength
210nm, 30 DEG C of column temperature.
Embodiment 4
Detection method
(1) Multiple electrolytes injection (II) sample 100ml is taken, adds hydrochloric acid 2ml to be uniformly mixed, water bath method is cooled to
After room temperature plus water 3ml redissolves.Wherein 2ml is taken, is set in test tube, acetone 5ml is added, is vortexed 1 minute, filtering takes filtrate water bath method,
It is cooled to room temperature, adds mobile phase 3ml ultrasound 2 minutes, filter to get test sample.
(2) hand that cellulose-three (3,5- dichlorophenyl carbamate) is stationary phase is covalently bonded with Silica Surface
Property chromatographic column, using n-hexane: isopropanol: dehydrated alcohol: trifluoroacetic acid=80:10:10:0.1 is mobile phase, Detection wavelength
210nm, 30 DEG C of column temperature.
Comparative example 1
Comparison uses the effect of isopropyl alcohol extraction
Detection method
(1) Multiple electrolytes injection (II) sample 100ml is taken, adds hydrochloric acid 2ml to be uniformly mixed, water bath method is cooled to
After room temperature plus water 3ml redissolves.Wherein 2ml is taken, is set in test tube, isopropanol 5ml is added, is vortexed 1 minute, filtering takes filtrate water-bath to steam
It is dry, it is cooled to room temperature, adds mobile phase 3ml ultrasound 2 minutes, filter to get test sample.
(2) hand that cellulose-three (3,5- dichlorophenyl carbamate) is stationary phase is covalently bonded with Silica Surface
Property chromatographic column, using n-hexane: isopropanol: dehydrated alcohol: trifluoroacetic acid=90:7:3:0.1 is mobile phase, Detection wavelength 210nm,
30 DEG C of column temperature.
Comparative example 2
Detection method
(1) Multiple electrolytes injection (II) sample 50ml is taken, adds hydrochloric acid 1ml to be uniformly mixed, water bath method is cooled to room
Wen Houjia water 1ml redissolves.Wherein 1ml is taken, is set in test tube, acetone 2ml is added, is vortexed 1 minute, filtering takes filtrate water bath method, cold
But to room temperature, add mobile phase 3ml ultrasound 2 minutes, filter to get test sample.
(2) hand that cellulose-three (3,5- dichlorophenyl carbamate) is stationary phase is covalently bonded with Silica Surface
Property chromatographic column, using n-hexane: isopropanol: dehydrated alcohol: trifluoroacetic acid=90:7:3:0.1 is mobile phase, Detection wavelength 210nm,
30 DEG C of column temperature.
Comparative example 3
Detection method
(1) Multiple electrolytes injection (II) sample 600ml is taken, adds hydrochloric acid 7ml to be uniformly mixed, water bath method is cooled to
After room temperature plus water 7ml redissolves.Wherein 2ml is taken, is set in test tube, acetone 12ml is added, is vortexed 1 minute, filtering takes filtrate water-bath to steam
It is dry, it is cooled to room temperature, adds mobile phase 3ml ultrasound 2 minutes, filter to get test sample.
(2) hand that cellulose-three (3,5- dichlorophenyl carbamate) is stationary phase is covalently bonded with Silica Surface
Property chromatographic column, using n-hexane: isopropanol: dehydrated alcohol: trifluoroacetic acid=90:7:3:0.1 is mobile phase, Detection wavelength 210nm,
30 DEG C of column temperature.
Test result:
As shown in Figure 1, L MALIC ACID and D-malic acid separating degree are good in the detection method of embodiment 1, and do not have inorganic salts
Testing result is interfered with water.
As shown in Figure 2, mobile phase polarity is smaller in the detection method of embodiment 2, L MALIC ACID and D-malic acid separating degree
Preferably, but retention time is longer, and detection efficiency reduces.
From the figure 3, it may be seen that L MALIC ACID and D-malic acid are since mobile phase polarity is larger in the detection method of embodiment 3
It can not be kept completely separate.
The testing result of embodiment 4 also shows L MALIC ACID and D-malic acid and can not be kept completely separate.
The test result of embodiment 2~4 shows that the polarity of mobile phase imitates the separating degree of L MALIC ACID isomers and separation
Rate also has a larger impact, and mobile phase each group distribution ratio of the present invention being capable of separation to L MALIC ACID isomers and detection band
Carry out beneficial effect.
As shown in Figure 4, pre-treatment is carried out to sample using isopropanol in comparative example 1, makes L MALIC ACID peak in testing result
Type is poor, shows that solvent effect is obvious.Occurs biggish impurity peaks (isopropanol introducing) Interference Detection before L MALIC ACID.
2 taken Multiple electrolytes injection (II) sample of comparative example is less than 100ml test sample in detection below
Concentration is too low, influences the detection sensitivity of isomers, and the sampling of comparative example 3 can then introduce a large amount of inorganic salts rear greater than 500ml
It cannot exclude the interference of inorganic salts in continuous processing.
The amount that hydrochloric acid is added in preceding processing, which is less than 2ml, to exclude the acetate in inorganic salts completely, be greater than 5ml wave
Take reagent to pre-treatment without improvement.
The dosage of redissolution water, which is less than 2ml, can not then be completely dissolved remaining sample, be greater than 5ml then when with acetone extract
Precipitating can not be formed.
Acetone dosage, which is less than 3ml, can not form the interference for precipitating and then excluding inorganic salts, be greater than 10ml waste reagent to preceding
Processing is without improvement.
Claims (6)
1. the detection method of L MALIC ACID isomers in a kind of Multiple electrolytes injection (II), it is characterised in that the detection method
Specifically comprise the following steps:
(1) a certain amount of Multiple electrolytes injection (II) sample is taken, appropriate concentrated hydrochloric acid is added to be uniformly mixed, water bath method is cooling
After to room temperature plus water redissolves.Wherein 2ml is taken, is set in test tube, acetone is added, is vortexed 1 minute, filtering takes filtrate water bath method, cooling
To room temperature, add mobile phase 3ml ultrasound 2 minutes, filters to get test sample.
(2) the chiral color that cellulose-three (3,5- dichlorophenyl carbamate) is stationary phase is covalently bonded with Silica Surface
Column is composed, using n-hexane: isopropanol: dehydrated alcohol: trifluoroacetic acid is mobile phase, Detection wavelength 210nm, and 30 DEG C of column temperature.
2. Multiple electrolytes injection (II) as described in claim 1, is containing sodium chloride, potassium chloride, magnesium chloride, chlorination
The aqueous solution of calcium, sodium acetate and L MALIC ACID.It is characterized in that the sampling amount of compound electrolyte injection (II) be 100ml~
500ml, preferably 200ml.
3. L MALIC ACID isomery body detecting method as described in claim 1, it is characterised in that the pre-treatment is used with concentrated hydrochloric acid
Amount is 2ml~5ml, preferably 2ml.
4. L MALIC ACID isomery body detecting method as described in claim 1, it is characterised in that the dosage of redissolution water is
2ml~5ml, preferably 3ml.
5. L MALIC ACID isomery body detecting method as described in claim 1, it is characterised in that the acetone before the vortex is used
Amount is 3ml~10ml, preferably 3ml.
6. L MALIC ACID isomery body detecting method as described in claim 1, it is characterised in that n-hexane ratio in the mobile phase
Example is 80%~95%, preferably 90%;Isopropanol ratios are 0%~10%, preferably 7%;Dehydrated alcohol ratio be 0%~
10%, preferably 3%;Trifluoroacetic acid ratio is 0.1%.
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CN113274350A (en) * | 2021-04-22 | 2021-08-20 | 石家庄四药有限公司 | Compound electrolyte injection and preparation method thereof |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
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CN110522763A (en) * | 2019-10-08 | 2019-12-03 | 四川太平洋药业有限责任公司 | A kind of Multiple electrolytes injection and preparation process |
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