CN110174474B - Method for detecting L-malic acid isomer in compound electrolyte injection (II) - Google Patents
Method for detecting L-malic acid isomer in compound electrolyte injection (II) Download PDFInfo
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- CN110174474B CN110174474B CN201910441800.XA CN201910441800A CN110174474B CN 110174474 B CN110174474 B CN 110174474B CN 201910441800 A CN201910441800 A CN 201910441800A CN 110174474 B CN110174474 B CN 110174474B
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- G—PHYSICS
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- 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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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- G01N30/02—Column chromatography
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- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
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- G01N2030/126—Preparation by evaporation evaporating sample
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Abstract
The invention provides a method for detecting an L-malic acid isomer in a compound electrolyte injection (II), which comprises the following steps: the compound electrolyte injection (II) sample is pretreated by hydrochloric acid and acetone, the interference of inorganic salt and water in the sample on L-malic acid is removed, and the content of L-malic acid isomer in the sample is determined by using a forward chromatography.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a method for detecting an L-malic acid isomer in a compound electrolyte injection (II).
Background
The compound electrolyte injection (II) is an aqueous solution containing sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium acetate and L-malic acid.
The malic acid is a molecule containing a chiral center, the L-malic acid and the D-malic acid are a pair of isomers, and documents show that the L-malic acid has important physiological functions, is an important intermediate product of internal circulation of a human body, is easy to be absorbed by the human body, can be used for treating various diseases such as liver diseases, anemia, low immunity, uremia, hypertension, liver failure and the like, and can relieve the toxic effect of an anticancer medicament on normal cells. But D-malic acid is physiologically ineffective. Therefore, an effective method is needed to be established for controlling the content of the D-malic acid in the compound electrolyte injection (II) so as to ensure the curative effect of the compound electrolyte injection (II).
The method for measuring the isomer in the L-malic acid raw material is reported in the document < normal phase high performance liquid chromatography for measuring enantiomer D-malic acid in L-malic acid > by Chaoxi, and the like. The method has certain specificity, is suitable for measuring the isomer in the malic acid bulk drug with single component, and the sample needs to be dissolved by normal phase diluent before measurement, so the method is not suitable for directly detecting the L-malic acid isomer in the compound electrolyte injection (II) with complex component.
The use of iodoethane-derived gas chromatography for the detection of malonic, succinic, tartaric, malic, adipic, glutaric and citric acids in wine and must has been reported by Duxi et al in the literature "derivatization gas chromatography for the determination of organic acids in wine and wine". According to the method, before the determination, the derivatization of a sample needs to be carried out, a large amount of inorganic salt contained in the compound electrolyte injection (II) interferes with the derivatization reaction, and finally the derivatization reaction cannot be carried out.
At present, no report on a detection method of L-malic acid isomer in the compound electrolyte injection (II) is found in domestic and foreign documents. Inorganic salt and water contained in the compound electrolyte injection (II) can interfere with the detection of the L-malic acid isomer, so that a new detection method needs to be established to effectively detect the content of the L-malic acid isomer in the compound electrolyte injection (II) so as to control the quality of the compound electrolyte injection (II).
Disclosure of Invention
The invention aims to provide a method for detecting L-malic acid isomer in compound electrolyte injection (II) aiming at the blank of the prior art, solves the problem of avoiding the interference of inorganic salt and water in the compound electrolyte injection (II) on the detection of the L-malic acid isomer, improves the sensitivity, specificity and accuracy of the detection method, and ensures that the detection method meets the requirement of quality control of industrial production.
The method for detecting the L-malic acid isomer in the compound electrolyte injection (II) specifically comprises the following steps:
(1) taking 100ml of a compound electrolyte injection (II) sample, adding a proper amount of concentrated hydrochloric acid, uniformly mixing, evaporating in a water bath, cooling to room temperature, and adding water for redissolution. Taking 2ml of the sample, placing the sample in a test tube, adding acetone, vortexing for 1 minute, filtering, taking the filtrate, evaporating the filtrate in a water bath to dryness, cooling to room temperature, adding mobile phase, performing ultrasonic treatment for 2 minutes, and filtering to obtain the sample.
(2) The method comprises the following steps of using a silica gel surface covalently bonded with cellulose-tris (3, 5-dichlorophenyl carbamate) as a chiral chromatographic column of a stationary phase, and using n-hexane: isopropyl alcohol: anhydrous ethanol: trifluoroacetic acid is used as a mobile phase, the detection wavelength is 210nm, and the column temperature is 30 ℃.
In the detection method, the compound electrolyte injection (II) is an aqueous solution containing sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium acetate and L-malic acid. The sample size is 100ml to 500ml, preferably 200 ml.
The amount of the concentrated hydrochloric acid for pretreatment is 2ml to 5ml, preferably 2 ml.
The amount of the redissolution water is 2ml to 5ml, preferably 3 ml.
The amount of acetone before vortexing is 3ml to 10ml, preferably 3 ml.
The proportion of the normal hexane in the mobile phase is 80-95%, preferably 90%; the proportion of isopropanol is 0 to 10 percent, preferably 7 percent; the proportion of the absolute ethyl alcohol is 0 to 10 percent, and the preference is 3 percent; the trifluoroacetic acid proportion was 0.1%.
In the invention, concentrated hydrochloric acid is adopted to be evaporated to dryness in a water bath in the pretreatment process of the compound electrolyte injection (II) sample, so that the interference of sodium acetate can be removed; adding acetone, whirling, filtering, removing the interference of other inorganic salts and water, and completely eliminating the detection of the inorganic salts and water in the compound electrolyte injection (II) on the L-malic acid isomer through two-step pretreatment.
In the sample detection process, a chiral column with cellulose-tris (3, 5-dichlorophenyl carbamate) as a filler is covalently bonded on the surface of silica gel, and compared with a coating type filler, the bonded filler has higher stability and stable retention time, and can effectively avoid the interference of other impurities in L-malic acid on isomers thereof.
The invention has the following advantages: 1. fills the blank of the detection method of the L-malic acid isomer in the compound electrolyte injection (II). 2. The interference of inorganic salt and water in the compound electrolyte injection (II) to the detection of the L-malic acid isomer is avoided, and the interference of other impurities is avoided by adopting a bonding filler chiral column in the detection.
Drawings
FIG. 1 liquid chromatogram of example 1 of the present invention
FIG. 2 liquid chromatogram of example 2 of the present invention
FIG. 3 liquid chromatogram of example 3 of the present invention
FIG. 4 liquid chromatogram of comparative example 1 of the present invention
Detailed Description
The following examples are intended to illustrate the invention in detail, but are not intended to limit the invention.
Example 1
Detection method
(1) Taking 200ml of a compound electrolyte injection (II) sample, adding 2ml of hydrochloric acid, uniformly mixing, evaporating in a water bath, cooling to room temperature, and adding 3ml of water for redissolution. Taking 2ml of the solution, placing the solution in a test tube, adding 3ml of acetone, swirling for 1 minute, filtering, taking the filtrate, evaporating in a water bath, cooling to room temperature, adding 3ml of mobile phase, performing ultrasonic treatment for 2 minutes, and filtering to obtain the sample.
(2) The method comprises the following steps of using a silica gel surface covalently bonded with cellulose-tris (3, 5-dichlorophenyl carbamate) as a chiral chromatographic column of a stationary phase, and using n-hexane: isopropyl alcohol: anhydrous ethanol: trifluoroacetic acid (90: 7:3: 0.1) as a mobile phase, a detection wavelength of 210nm and a column temperature of 30 ℃.
Example 2
Detection method
(1) Taking 300ml of a compound electrolyte injection (II) sample, adding 5ml of hydrochloric acid, uniformly mixing, evaporating in a water bath, cooling to room temperature, and adding 2ml of water for redissolution. Taking 2ml of the solution, placing the solution in a test tube, adding 3ml of acetone, swirling for 1 minute, filtering, taking the filtrate, evaporating in a water bath, cooling to room temperature, adding 3ml of mobile phase, performing ultrasonic treatment for 2 minutes, and filtering to obtain the sample.
(2) The method comprises the following steps of using a silica gel surface covalently bonded with cellulose-tris (3, 5-dichlorophenyl carbamate) as a chiral chromatographic column of a stationary phase, and using n-hexane: isopropyl alcohol: anhydrous ethanol: trifluoroacetic acid 95:5:0:0.1 as mobile phase, detecting wavelength 210nm, column temperature 30 ℃.
Example 3
Detection method
(1) Taking 500ml of a compound electrolyte injection (II) sample, adding 3.5ml of hydrochloric acid, uniformly mixing, evaporating in a water bath, cooling to room temperature, and adding 5ml of water for redissolution. Taking 2ml of the solution, placing the solution in a test tube, adding 10ml of acetone, swirling for 1 minute, filtering, taking the filtrate, evaporating in a water bath, cooling to room temperature, adding 3ml of mobile phase, performing ultrasonic treatment for 2 minutes, and filtering to obtain the sample.
(2) The method comprises the following steps of using a silica gel surface covalently bonded with cellulose-tris (3, 5-dichlorophenyl carbamate) as a chiral chromatographic column of a stationary phase, and using n-hexane: isopropyl alcohol: anhydrous ethanol: trifluoroacetic acid (80: 10:10: 0.1) as a mobile phase, a detection wavelength of 210nm and a column temperature of 30 ℃.
Example 4
Detection method
(1) Taking 100ml of a compound electrolyte injection (II) sample, adding 2ml of hydrochloric acid, uniformly mixing, evaporating in a water bath, cooling to room temperature, and adding 3ml of water for redissolution. Taking 2ml of the solution, placing the solution in a test tube, adding 5ml of acetone, swirling for 1 minute, filtering, taking the filtrate, evaporating in a water bath, cooling to room temperature, adding 3ml of mobile phase, performing ultrasonic treatment for 2 minutes, and filtering to obtain the sample.
(2) The method comprises the following steps of using a silica gel surface covalently bonded with cellulose-tris (3, 5-dichlorophenyl carbamate) as a chiral chromatographic column of a stationary phase, and using n-hexane: isopropyl alcohol: anhydrous ethanol: trifluoroacetic acid (80: 10:10: 0.1) as a mobile phase, a detection wavelength of 210nm and a column temperature of 30 ℃.
Comparative example 1
Comparison of the Effect of extraction with isopropanol
Detection method
(1) Taking 100ml of a compound electrolyte injection (II) sample, adding 2ml of hydrochloric acid, uniformly mixing, evaporating in a water bath, cooling to room temperature, and adding 3ml of water for redissolution. Taking 2ml of the solution, placing the solution in a test tube, adding 5ml of isopropanol, swirling for 1 minute, filtering, taking the filtrate, evaporating in a water bath, cooling to room temperature, adding 3ml of mobile phase, performing ultrasonic treatment for 2 minutes, and filtering to obtain the sample.
(2) The method comprises the following steps of using a silica gel surface covalently bonded with cellulose-tris (3, 5-dichlorophenyl carbamate) as a chiral chromatographic column of a stationary phase, and using n-hexane: isopropyl alcohol: anhydrous ethanol: trifluoroacetic acid (90: 7:3: 0.1) as a mobile phase, a detection wavelength of 210nm and a column temperature of 30 ℃.
Comparative example 2
Detection method
(1) Taking 50ml of a compound electrolyte injection (II) sample, adding 1ml of hydrochloric acid, uniformly mixing, evaporating in a water bath, cooling to room temperature, and adding 1ml of water for redissolution. Taking 1ml of the solution, placing the solution in a test tube, adding 2ml of acetone, swirling for 1 minute, filtering, taking the filtrate, evaporating in a water bath, cooling to room temperature, adding 3ml of mobile phase, performing ultrasonic treatment for 2 minutes, and filtering to obtain the sample.
(2) The method comprises the following steps of using a silica gel surface covalently bonded with cellulose-tris (3, 5-dichlorophenyl carbamate) as a chiral chromatographic column of a stationary phase, and using n-hexane: isopropyl alcohol: anhydrous ethanol: trifluoroacetic acid (90: 7:3: 0.1) as a mobile phase, a detection wavelength of 210nm and a column temperature of 30 ℃.
Comparative example 3
Detection method
(1) Taking 600ml of a compound electrolyte injection (II) sample, adding 7ml of hydrochloric acid, uniformly mixing, evaporating in a water bath, cooling to room temperature, and adding 7ml of water for redissolution. Taking 2ml of the solution, placing the solution in a test tube, adding 12ml of acetone, swirling for 1 minute, filtering, taking the filtrate, evaporating in a water bath, cooling to room temperature, adding 3ml of mobile phase, performing ultrasonic treatment for 2 minutes, and filtering to obtain the sample.
(2) The method comprises the following steps of using a silica gel surface covalently bonded with cellulose-tris (3, 5-dichlorophenyl carbamate) as a chiral chromatographic column of a stationary phase, and using n-hexane: isopropyl alcohol: anhydrous ethanol: trifluoroacetic acid (90: 7:3: 0.1) as a mobile phase, a detection wavelength of 210nm and a column temperature of 30 ℃.
And (3) test results:
as can be seen from FIG. 1, the separation degree of L-malic acid and D-malic acid in the detection method of example 1 was good, and no interference of inorganic salts and water on the detection results was observed.
As can be seen from FIG. 2, in the detection method of example 2, the polarity of the mobile phase is small, the separation degree of L-malic acid and D-malic acid is good, but the retention time is long, and the detection efficiency is reduced.
As can be seen from FIG. 3, in the detection method of example 3, the L-malic acid and D-malic acid could not be completely separated due to the large polarity of the mobile phase.
The test results of example 4 also showed that L-malic acid and D-malic acid could not be completely separated.
The test results of the embodiments 2 to 4 show that the polarity of the mobile phase also has a great influence on the separation degree and the separation efficiency of the L-malic acid isomer, and the distribution ratio of the components of the mobile phase can bring a beneficial effect on the separation and the detection of the L-malic acid isomer.
As can be seen from FIG. 4, in comparative example 1, the sample was pretreated with isopropanol, so that the peak pattern of L-malic acid in the detection result was poor, indicating that the solvent effect was significant. The presence of a large impurity peak (isopropanol incorporation) in front of the L-malic acid interfered with the detection.
The concentration of the compound electrolyte injection (II) sampled by the sample of less than 100ml in the comparative example 2 in the subsequent detection is too low, so that the detection sensitivity of isomers is influenced, and the sample of more than 500ml in the comparative example 3 introduces a large amount of inorganic salt which cannot eliminate the interference of the inorganic salt in the subsequent treatment.
The addition of hydrochloric acid in an amount of less than 2ml in the pretreatment can not completely remove acetate in inorganic salt, and the waste of more than 5ml of reagents has no improvement on the pretreatment.
The amount of reconstitution water used was less than 2ml and failed to completely dissolve the remaining sample, and more than 5ml failed to form a precipitate upon extraction with acetone.
The acetone dosage is less than 3ml, so that no precipitate can be formed, the interference of inorganic salt is eliminated, and more than 10ml of reagent is wasted, so that the pretreatment is not improved.
Claims (10)
1. A detection method of L-malic acid isomer in compound electrolyte injection (II), the compound electrolyte injection (II) is an aqueous solution containing sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium acetate and L-malic acid, and is characterized in that the detection method specifically comprises the following steps:
(1) taking a certain amount of compound electrolyte injection (II) sample, adding a proper amount of concentrated hydrochloric acid, uniformly mixing, evaporating to dryness in a water bath, cooling to room temperature, adding water for redissolving, taking 2ml of the mixture, placing the mixture in a test tube, adding acetone, carrying out vortex for 1 minute, filtering, taking filtrate, evaporating to dryness in a water bath, cooling to room temperature, adding 3ml of mobile phase, carrying out ultrasonic treatment for 2 minutes, and filtering to obtain a test sample;
(2) the method comprises the following steps of using a silica gel surface covalently bonded with cellulose-tris (3, 5-dichlorophenyl carbamate) as a chiral chromatographic column of a stationary phase, and using n-hexane: isopropyl alcohol: anhydrous ethanol: trifluoroacetic acid is used as a mobile phase, the detection wavelength is 210nm, and the column temperature is 30 ℃; the proportion of normal hexane in the mobile phase is 80-95%, the proportion of isopropanol is 0-10%, the proportion of absolute ethyl alcohol is 3%, and the proportion of trifluoroacetic acid is 0.1%.
2. The detection method according to claim 1, wherein the sample volume of the compound electrolyte injection (II) is 100ml to 500 ml.
3. The detection method according to claim 1, wherein the amount of the concentrated hydrochloric acid is 2ml to 5 ml.
4. The detection method according to claim 1, wherein the amount of the reconstitution water is 2ml to 5 ml.
5. The assay of claim 1 wherein the amount of acetone used prior to vortexing is between 3ml and 10 ml.
6. The detection method according to claim 1, wherein the proportion of n-hexane in the mobile phase is 90%.
7. The detection method according to claim 1, wherein the ratio of isopropyl alcohol in the mobile phase is 7%.
8. The assay of claim 2 wherein said compound electrolyte injection (ii) is sampled at 200 ml.
9. The assay of claim 3 wherein said concentrated hydrochloric acid is present in an amount of 2 ml.
10. The assay of claim 1 wherein said amount of acetone prior to vortexing is 3 ml.
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| US20050187210A1 (en) * | 2003-02-24 | 2005-08-25 | Atsushi Ozaki | Method for treating severe heart failure and medicament therefor |
| CN109030656A (en) * | 2018-08-17 | 2018-12-18 | 华仁药业股份有限公司 | Detection method of the glucose in relation to substance in acetate Multiple electrolytes injection |
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| US20050187210A1 (en) * | 2003-02-24 | 2005-08-25 | Atsushi Ozaki | Method for treating severe heart failure and medicament therefor |
| CN109030656A (en) * | 2018-08-17 | 2018-12-18 | 华仁药业股份有限公司 | Detection method of the glucose in relation to substance in acetate Multiple electrolytes injection |
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| Malate quinoneoxidoreductasebiosensorsbasedon tetrathiafulvalene andgoldnanoparticlesmodifiedscreen-printed carbon electrodesformalicaciddeterminationinwine;Bego˜na Molinero-Abad等;《Sensors andActuatorsB:Chemical》;20141231;全文 * |
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