CN109187829A - The discrimination method of polyoxyethylene sorbitan monoleate in injection and Shenmai injection - Google Patents
The discrimination method of polyoxyethylene sorbitan monoleate in injection and Shenmai injection Download PDFInfo
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- CN109187829A CN109187829A CN201811051028.2A CN201811051028A CN109187829A CN 109187829 A CN109187829 A CN 109187829A CN 201811051028 A CN201811051028 A CN 201811051028A CN 109187829 A CN109187829 A CN 109187829A
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- polyoxyethylene sorbitan
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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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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- 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
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Abstract
The present invention provides the discrimination methods of polyoxyethylene sorbitan monoleate in injection and Shenmai injection.Discrimination method, including the following steps: step A: injection to be measured is heated at 90~150 DEG C, is then inverted the container for filling the injection to be measured, when being cooled to 75 DEG C or more, then is quenched to 50 DEG C hereinafter, standing and is precipitated completely to polyoxyethylene sorbitan monoleate；Step B: being saponified the polyoxyethylene sorbitan monoleate that the step A is precipitated, pre-column derivatization, then using the content of oleic acid in chromatography detection polyoxyethylene sorbitan monoleate.The present invention can effectively extract the polyoxyethylene sorbitan monoleate in injection, establish reliable basis for the accurate quality for identifying polyoxyethylene sorbitan monoleate, and method specificity is strong, as a result reliably.
Description
Technical field
The present invention relates to quality standard technical fields, more particularly, to polyoxyethylene sorbitan monoleate in injection and Shenmai injection
Discrimination method.
Background technique
Chinese Pharmacopoeia in 2015 increases polyoxyethylene sorbitan monoleate (injection) quality standard, the standard and polyoxyethylene sorbitan monoleate matter
There is biggish difference on the basis of amount standard substance.
Polyoxyethylene sorbitan monoleate (injection) standard fatty acid composition regulation: oleic acid composition is not less than 98%, myristic acid, palm fibre
Palmitic acid acid, palmitoleic acid, stearic acid, linoleic acid, linolenic acid content must not cross 0.5%.
Polyoxyethylene sorbitan monoleate standard substance standard fatty acid composition regulation: oleic acid composition is not less than 58%, myristic acid, palm
Acid, palmitoleic acid, stearic acid, linoleic acid, linolenic acid be not greater than 5.0% respectively, 16.0%, 8.0%, 6.0%, 18.0%,
4.0%.
Above two polyoxyethylene sorbitan monoleate market price difference is very big, and about 2000 yuan of polyoxyethylene sorbitan monoleate (injection) price/
Kg；About 40 yuan/Kg of polyoxyethylene sorbitan monoleate price.
Traditional Chinese medicine is more using the kind of polyoxyethylene sorbitan monoleate, such as: Shenmai injection, shengmai injection, cordate houttuynia note
Liquid etc. is penetrated, the solubilising of medical fluid is mainly used for.
It (whether is the poly- mountain of injection there is presently no the identification report about polyoxyethylene sorbitan monoleate auxiliary material in traditional Chinese medicine
Pear ester 80).Therefore establish the polyoxyethylene sorbitan monoleate that is added in traditional Chinese medicine whether be injection auxiliary material method, facilitate
Auxiliary material addition is normative in medicine injection, provides foundation for quality evaluation.
In view of this, the present invention is specifically proposed.
Summary of the invention
The first object of the present invention is the discrimination method of polyoxyethylene sorbitan monoleate in injection, and this method can be extracted effectively
Polyoxyethylene sorbitan monoleate in injection establishes reliable basis for the accurate quality for identifying polyoxyethylene sorbitan monoleate.
The second object of the present invention is the discrimination method of polyoxyethylene sorbitan monoleate in Shenmai injection, and this method can be mentioned effectively
The polyoxyethylene sorbitan monoleate in Shenmai injection is taken out, establishes reliable basis for the accurate quality for identifying polyoxyethylene sorbitan monoleate, and square
Method specificity is strong, as a result reliably.
In order to achieve the goal above, the present invention provides following technical schemes:
The discrimination method of polyoxyethylene sorbitan monoleate in injection, including the following steps:
Step A: injection to be measured is heated at 90~150 DEG C, is then inverted the container for filling the injection to be measured, cold
When but to 75 DEG C or more, then it is quenched to 50 DEG C hereinafter, standing and is precipitated completely to polyoxyethylene sorbitan monoleate；
Step B: being saponified the polyoxyethylene sorbitan monoleate that the step A is precipitated, pre-column derivatization, then poly- using chromatography detection
The content of oleic acid in sorb ester 80.
Firstly, the present invention using oleic acid content as the foundation for identifying polyoxyethylene sorbitan monoleate quality, is according to injection in the market
Find that the oleic acid content of two kinds of products has marked difference depending on the common difference in quality with polyoxyethylene sorbitan monoleate, in research.
Commercially available polyoxyethylene sorbitan monoleate oleic acid composition (three producers) is detected, as a result see the table below 1.As can be seen from the table, different
The commercially available polyoxyethylene sorbitan monoleate oleic acid composition content difference of producer is big, in 77%~88% range.Show commercially available polyoxyethylene sorbitan monoleate oil
Sour composition ratio differs greatly.
The commercially available polyoxyethylene sorbitan monoleate oleic acid of table 1 forms content detection result (n=3)
| Number | Oleic acid forms content |
| Producer A | 77.9% ± 0.20% |
| Producer B | 83.2% ± 0.15% |
| Producer C | 85.7% ± 0.18% |
Commercially available polysorbate (injection) oleic acid composition is detected, as a result the product oleic acid content is 98.8% ± 0.12% (n
=3).Injection polyoxyethylene sorbitan monoleate oleic acid composition ratio is high.
To sum up, using oleic acid content as the foundation for identifying polyoxyethylene sorbitan monoleate quality.
Secondly, the prior art discloses only the method for identifying content of fatty acid in polyoxyethylene sorbitan monoleate, there is no it is open from
The method of polyoxyethylene sorbitan monoleate is extracted in practical drug.However, the identification for polyoxyethylene sorbitan monoleate in actual product, extraction process is
It is the basis for guaranteeing identification result accuracy, specificity.
Above method of the invention overcomes polyoxyethylene sorbitan monoleate in injection and extracts difficult problem, is risen using polyoxyethylene sorbitan monoleate
The principle being layered in medical fluid after covered with clouds can easily separate polyoxyethylene sorbitan monoleate from medical fluid.
Specifically, there is phenomenon covered with clouds (solutions turbid) after polyoxyethylene sorbitan monoleate solution (by taking injection as an example) high-temperature heating,
Temperature can become clarification when restoring.After actually sterilizing, rise it is covered with clouds after polyoxyethylene sorbitan monoleate solution, stood, cooling, meeting in medical fluid
There is polyoxyethylene sorbitan monoleate to be unevenly distributed, the phenomenon that lower layer is more, upper layer is few occurs, isolated polyoxyethylene sorbitan monoleate using this phenomenon.
In addition, judging standard according to the condition of production of injection Polysorbate 80 currently on the market, can be used as follows
Standard: when oleic acid content is greater than 97%, to add polyoxyethylene sorbitan monoleate (injection) auxiliary material Shenmai injection；Oleic acid content is less than
90% is addition polyoxyethylene sorbitan monoleate ordinary adjuvants Shenmai injection.
Rotten generally for chemical component is avoided, high-temperature heating preferably uses the means of steam sterilizing.
In the present invention, it is the polyoxyethylene sorbitan monoleate for extracting high-purity, needs to control the keys such as heating temperature, cooling temperature
Parameter.
When the present invention extracts polyoxyethylene sorbitan monoleate from injection, preferably use ampoule bottled, detailed process are as follows:
Injection to be measured is heated at 90~150 DEG C, the ampoule bottle for filling the injection to be measured is then inverted, is cooled to
It at 75 DEG C or more, then is quenched to 50 DEG C hereinafter, standing and is precipitated completely to polyoxyethylene sorbitan monoleate, polyoxyethylene sorbitan monoleate is attached to ampoule at this time
Bottle head, taking-up (can lead to common solvent dissolution).
The purpose of step A of the present invention is that the polyoxyethylene sorbitan monoleate of injection is made to be layered precipitation, therefore heating time, cooling completely
Temperature range and time of repose are complete be precipitated to investigate purpose.
The process of pre-column derivatization matches with chromatographic means in the present invention, before homochromatography does not match different columns
Derivatization method.
The identification of the discrimination method of the invention polysorbate-80 for injection suitable for all kinds of injections, such as common ginseng
Wheat injection, shengmai injection, ginseng aconite injection liquid etc..
On the basis of above, discrimination method of the invention can also be further improved, specific as follows.
Preferably, the chromatography gas chromatography, chromatographic condition are as follows:
Chromatographic column: 85~95% cyanogen propyl polysiloxanes are the quartz capillary column of fixer,
Originating column temperature is 85~95 DEG C, is warming up to 150~170 DEG C with 15~25 DEG C of rate per minute, then with per minute
1.5~2.5 DEG C of rate is warming up to 210~230 DEG C,
320~360 DEG C of injector temperature,
Detector is flame ionization ditector, 310~350 DEG C of temperature,
Number of theoretical plate is calculated by methyl oleate peak 10000 or more.
Specificity, precision, the reproducibility of the above gas chromatography are more preferable, and the rate of recovery with higher, detection limit
It is low.Therefore it is sensitiveer, accurate, reliable polyoxyethylene sorbitan monoleate to be identified using above method.
Preferably, the chromatographic condition are as follows: chromatographic column: 85~88% cyanogen propyl polysiloxanes are the quartzy capillary of fixer
Tubing string,
Preferably, starting column temperature is 85~90 DEG C, is warming up to 160~170 DEG C with 15~20 DEG C of rate per minute, then with
1.5~2 DEG C of rate per minute is warming up to 210~220 DEG C,
Preferably, 320~340 DEG C of injector temperature,
Preferably, detector is flame ionization ditector, 310~330 DEG C of temperature.
Preferably, when the detection, oleic acid content is calculated using area normalization method.
It is simple, quick that content is calculated using area normalization method.
Preferably, reference substance used when the detection are as follows: methyl myristate, methyl hexadecanoate, Methyl palmitoleinate,
Methyl stearate, methyl linoleate, methyl linolenate and methyl oleate.
Preferably, the method for the saponification are as follows: in the methanol solution environment containing 1.5~2.5% sodium hydroxides, heat back
Stream reaction.
Using this saponification method fully reacting, polyoxyethylene sorbitan monoleate can be made more fully saponified.
It is highly preferred that in the methanol solution environment containing 2~2.5% sodium hydroxides, heating reflux reaction.
Preferably, the method for the pre-column derivatization are as follows: boron trifluoride methyl esterization, preferably are as follows:
Containing heating reflux reaction in 10~15% boron trifluoride methanol solution；
Preferably, containing heating reflux reaction in 10~14% boron trifluoride methanol solution；
Pre-column derivatization esterification yield in the above conditions is higher, can reach 98% or more.
Preferably, after the pre-column derivatization and before the detection further include: extracted with normal heptane.
Preferably, detecting solvent used when the reference substance is normal heptane.
Solubility of the polyoxyethylene sorbitan monoleate in normal heptane is high, and the interference that normal heptane detects chromatography is small, ties detection
Fruit is more acurrate.
The discrimination method of the present invention various schemes described above is suitable for any type of injection, such as common ginseng wheat
Injection.
For Shenmai injection, the heating time in the step A is preferably 10min or more；
Preferably, 75 DEG C are cooled to described in the step A the above are be cooled to 75~95 DEG C；
Preferably, the time of standing described in the step A is within 0.5 hour.
To sum up, compared with prior art, invention achieves following technical effects:
(1) method that polyoxyethylene sorbitan monoleate is extracted from injection is simple, and recovery rate is high, purity is high；
(2) specificity for identifying polyoxyethylene sorbitan monoleate in injection is strong, and high sensitivity, precision are high, reproducible, is applicable in model
Enclose it is wide, can be used for Shenmai injection, shengmai injection, in ginseng aconite injection liquid polyoxyethylene sorbitan monoleate identification.
Detailed description of the invention
It, below will be to specific in order to illustrate more clearly of the specific embodiment of the invention or technical solution in the prior art
Embodiment or attached drawing needed to be used in the description of the prior art be briefly described, it should be apparent that, it is described below
Attached drawing is some embodiments of the present invention, for those of ordinary skill in the art, before not making the creative labor
It puts, is also possible to obtain other drawings based on these drawings.
Fig. 1 is the attachment state of Shenmai injection ampoule bottle head polyoxyethylene sorbitan monoleate after heating provided in an embodiment of the present invention
Figure；
Fig. 2 is that polyoxyethylene sorbitan monoleate provided in an embodiment of the present invention joins wheat extract oleic acid composition map；
Fig. 3 is that polyoxyethylene sorbitan monoleate provided in an embodiment of the present invention (injection) joins wheat extract oleic acid composition map.
Specific embodiment
Technical solution of the present invention is clearly and completely described below in conjunction with the drawings and specific embodiments, but
Be it will be understood to those of skill in the art that it is following described embodiments are some of the embodiments of the present invention, rather than it is whole
Embodiment is merely to illustrate the present invention, and is not construed as limiting the scope of the invention.Based on the embodiments of the present invention, ability
Domain those of ordinary skill every other embodiment obtained without making creative work, belongs to guarantor of the present invention
The range of shield.The person that is not specified actual conditions in embodiment, carries out according to conventional conditions or manufacturer's recommended conditions.Agents useful for same
Or production firm person is not specified in instrument, is the conventional products that can be obtained by commercially available purchase.
Experimental example 1
Study influence of the heating time to polyoxyethylene sorbitan monoleate is extracted
Shenmai injection 9 (10mL specification, ampoule are bottled) is taken, is divided into 3 groups, every group 3, is inverted, at 115 DEG C respectively
5min, 10min, 20min are heated, when medical fluid is cooled to 80 DEG C, is inverted and takes out, with 30 DEG C or so water elution coolings, waits 0.5
Ampoule bottle is just being put after hour, is observing ampoule bottle head polyoxyethylene sorbitan monoleate adhesion amount.As a result the sample ampoules of above-mentioned 3 kinds of heating times
Bottle head polyoxyethylene sorbitan monoleate adhesion amount is almost the same.
Experimental example 2
Study influence of the heating temperature to polyoxyethylene sorbitan monoleate is extracted
Shenmai injection 9 (10mL specification, ampoule are bottled) is taken, is divided into 3 groups, every group 3, is inverted, in 100 DEG C, 115
DEG C, heat 10min respectively at 121 DEG C, when medical fluid is cooled to 80 DEG C, is inverted and takes out, with 30 DEG C or so water elution coolings, wait
Ampoule bottle is just being put after 0.5 hour, is observing ampoule bottle head polyoxyethylene sorbitan monoleate adhesion amount.As a result the sample of above-mentioned 3 kinds of heating temperatures
Ampoule bottle head, 100 DEG C of heating condition polyoxyethylene sorbitan monoleate adhesion amounts are less, polyoxyethylene sorbitan monoleate is attached under 115 DEG C and 121 DEG C of heating conditions
Amount it is more and adhesion amount is almost the same.Illustrate that heating temperature has certain influence to the extracted amount of polyoxyethylene sorbitan monoleate tween, selects 115
DEG C be optimum heating temperature.
Experimental example 3
Study influence of the natural cooling time to polyoxyethylene sorbitan monoleate is extracted
Shenmai injection 9 (10mL specification, ampoule are bottled) is taken, is divided into 3 groups, every group 3, is inverted, is heated at 115 DEG C
10min, above-mentioned three groups of samples when being cooled to 50 DEG C, 75 DEG C, 95 DEG C respectively, are inverted and are taken out, and are cooled down with 30 DEG C or so water elution,
Ampoule bottle is just being put after waiting 0.5 hour, is observing ampoule bottle head polyoxyethylene sorbitan monoleate adhesion amount.As a result the sample of above-mentioned cooling temperature
Ampoule bottle head is cooled to 50 DEG C of sample polyoxyethylene sorbitan monoleate adhesion amounts and almost loses, is cooled to 75 DEG C and 95 DEG C of sample polysorbates
80 adhesion amounts are more and adhesion amount is almost the same.Illustrate that cooling temperature has certain influence to the extracted amount of polyoxyethylene sorbitan monoleate tween, selects
Selecting 75 DEG C, the above are best cooling outlet temperatures.
Experimental example 4
Study influence of the time of repose to polyoxyethylene sorbitan monoleate is extracted
Shenmai injection 9 (10mL specification, ampoule are bottled) is taken, is divided into 3 groups, every group 3, is inverted, is heated at 115 DEG C
10min when being cooled to 80 DEG C, is inverted and takes out, with the elution cooling of 30 DEG C or so water, wait respectively 0.5 hour, 1 hour, it is 2 small
When after ampoule bottle is just being put, observe ampoule bottle head polyoxyethylene sorbitan monoleate adhesion amount.As a result the sample ampoules bottle head of above-mentioned waiting time,
Wait 0.5 hour sample polyoxyethylene sorbitan monoleate adhesion amount at most, wait 1 hour sample polyoxyethylene sorbitan monoleate adhesion amount to reduce, wait it is 2 small
When sample polyoxyethylene sorbitan monoleate adhesion amount be further reduced.Illustrate that there is a fixing in the waiting time to the extracted amount of polyoxyethylene sorbitan monoleate tween
It rings, selecting waiting 0.5 hour is the best waiting time.
It can determine by the above experimental example, extract the preferred process parameter of polyoxyethylene sorbitan monoleate are as follows:
Heating time is 10min,
Heating temperature is 115 DEG C,
Natural cooling outlet temperature is 75 DEG C or more,
It is 0.5 hour that the waiting time is inverted after cooling.
Polyoxyethylene sorbitan monoleate in Shenmai injection is extracted using the condition, quality discrimination is carried out, is specifically shown in embodiment 1.
Embodiment 1
1, two kinds of Shenmai injections are prepared, a kind of auxiliary material is added to 0.5% polyoxyethylene sorbitan monoleate, and another auxiliary material is added to
0.5% polyoxyethylene sorbitan monoleate (injection).
Above two Shenmai injection sterilizes through 115 DEG C, 32min.
2, sample treatment:
Shenmai injection 60 (10mL specification, ampoule are bottled) is taken, is divided into 6 groups, every group 10, is inverted, adds at 115 DEG C
Hot 10min when being cooled to 80 DEG C, is inverted and takes out, and is cooled down with 30 DEG C or so water elution, by ampoule after waiting 0.5 hour respectively
Bottle just puts (result is as shown in Figure 1).Every group of 2% sodium hydrate methanol solution for using 5mL respectively dissolve to get.
2mL solution is drawn, is placed in 50mL conical flask, is set and be heated to reflux in water-bath 30 minutes, let cool, is added 14% borontrifluoride
Boron methanol solution 2mL is heated to reflux 30 minutes in a water bath, lets cool, and adds normal heptane 4mL, and continuation is heated to reflux 5 points in a water bath
Clock is let cool, and adds saturated sodium chloride solution 10mL, and shaking, standing makes to be layered, and is taken upper layer, is washed with water 3 times, uses distilled water every time
4mL, as test solution.
3, reference substance:
Methyl myristate, methyl hexadecanoate, Methyl palmitoleinate, methyl stearate, methyl linoleate, flax are taken respectively
Sour methyl esters and methyl oleate reference substance are appropriate, add normal heptane to dissolve and are made in every 1mL respectively containing the solution of 0.01g.
4, chromatographic condition and detection method:
It is tested according to gas chromatography (general rule 0521).Using 88% cyanogen propyl polysiloxanes as fixer (0.20 μ of thickness of liquid film
M) quartz capillary column (100m × 0.25mm) is chromatographic column, and starting column temperature is 90 DEG C and maintains 0 minute, with 20 DEG C per minute
Rate is warming up to 160 DEG C, maintains 1 minute, then is warming up to 220 DEG C with 2 DEG C of rate per minute, maintains 20 minutes；Injection port temperature
Spend 340 DEG C of detectors be flame ionization ditector, 330 DEG C of temperature.Number of theoretical plate is not less than by methyl oleate peak calculating
10000。
Detection: precision draws each 1 μ L of test solution and control solution, injects gas chromatograph, records chromatogram.It presses
Area normalization method is with calculated by peak area (ignoring peak of the peak area less than 0.05%) oleic acid content.
5, testing result
Above-mentioned sample oleic acid composition testing result see the table below, and the oleic acid that polyoxyethylene sorbitan monoleate extracts as can be known from Table 2 forms weight
Renaturation is fine.
2 Shenmai injection of table extracts oleic acid and forms study on the stability table
(2) Shenmai injection extracts polyoxyethylene sorbitan monoleate oleic acid composition measuring
The preparation of sample:
Commercially available three producer's polyoxyethylene sorbitan monoleates and a polyoxyethylene sorbitan monoleate (injection) are taken, presses Shenmai injection respectively
Legal preparation method prepares to obtain the Shenmai injection of 4 kinds of different auxiliary materials addition to get (10mL specification).
The preparation of test sample:
Shenmai injection 30 are taken, is divided into 3 groups, every group 10, is prepared according to repetitive research preparation method of test article,
To obtain the final product.
The preparation of reference substance solution, chromatographic condition and detection method are identical as repetitive research.
Testing result
Above-mentioned sample oleic acid composition testing result see the table below, the ginseng that the polyoxyethylene sorbitan monoleate of three producers is prepared as seen from the table
Wheat injection oleic acid composition content is low, in 77%~86% range；The ginseng wheat prepared using polyoxyethylene sorbitan monoleate (injection)
Injection oleic acid content is high, is greater than 97.0%.Illustrate Shenmai injection extract oleic acid made of two kinds of polyoxyethylene sorbitan monoleate auxiliary materials
Composition can be very good to distinguish the two there are marked difference.
The Shenmai injection of 3 different auxiliary material of table addition extracts oleic acid composition testing result (n=3)
Note: commercially available polyoxyethylene sorbitan monoleate (injection) only one producer, therefore only study producer's auxiliary material.
4, brief summary
(1) the oleic acid composition that polyoxyethylene sorbitan monoleate is sold in market has certain difference, in 77%~88% range.
(2) polysorbate (injection) oleic acid composition is greater than 98%.
(3) the polyoxyethylene sorbitan monoleate oleic acid composition detection extracted from Shenmai injection is stablized.
(4) the oleic acid composition for extracting the polyoxyethylene sorbitan monoleate and polyoxyethylene sorbitan monoleate (injection) that are added in Shenmai injection is deposited
In very big difference, and its oleic acid composition and original auxiliary material oleic acid composition are almost the same.
(5) it is directed to the studies above, it may be determined that use oleic acid compositions indicator, can easily identify from Shenmai injection
The polyoxyethylene sorbitan monoleate extracted is injection or non-injection liquid.
Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention., rather than its limitations；To the greatest extent
Pipe present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that: its according to
So be possible to modify the technical solutions described in the foregoing embodiments, or to some or all of the technical features into
Row equivalent replacement；And these are modified or replaceed, various embodiments of the present invention technology that it does not separate the essence of the corresponding technical solution
The range of scheme.
Claims (10)
1. the discrimination method of polyoxyethylene sorbitan monoleate in injection, characterized in that it comprises the following steps:
Step A: injection to be measured is heated at 90~150 DEG C, is then inverted the container for filling the injection to be measured, is cooled to
At 75 DEG C or more, then it is quenched to 50 DEG C hereinafter, standing and is precipitated completely to polyoxyethylene sorbitan monoleate；
Step B: the polyoxyethylene sorbitan monoleate that the step A is precipitated is saponified, pre-column derivatization, poly- sorb is then detected using chromatography
The content of oleic acid in ester 80.
2. discrimination method according to claim 1, which is characterized in that the chromatography gas chromatography, chromatographic condition are as follows:
Chromatographic column: 85~95% cyanogen propyl polysiloxanes are the quartz capillary column of fixer,
Originating column temperature is 85~95 DEG C, is warming up to 150~170 DEG C with 15~25 DEG C of rate per minute, then with per minute 1.5~
2.5 DEG C of rate is warming up to 210~230 DEG C,
320~360 DEG C of injector temperature,
Detector is flame ionization ditector, 310~350 DEG C of temperature,
Number of theoretical plate is calculated by methyl oleate peak 10000 or more.
3. discrimination method according to claim 1, which is characterized in that the chromatographic condition are as follows: chromatographic column: 85~88% cyanogen
Propyl polysiloxanes is the quartz capillary column of fixer,
Preferably, starting column temperature is 85~90 DEG C, is warming up to 160~170 DEG C with 15~20 DEG C of rate per minute, then with every point
The rate that 1.5~2 DEG C of clock is warming up to 210~220 DEG C,
Preferably, 320~340 DEG C of injector temperature,
Preferably, detector is flame ionization ditector, 310~330 DEG C of temperature.
4. discrimination method according to claim 1, which is characterized in that when the detection, calculated using area normalization method
Oleic acid content.
5. discrimination method according to claim 1, which is characterized in that reference substance used when the detection are as follows: nutmeg
Sour methyl esters, methyl hexadecanoate, Methyl palmitoleinate, methyl stearate, methyl linoleate, methyl linolenate and methyl oleate.
6. discrimination method according to claim 1, which is characterized in that the method for the saponification are as follows: containing 1.5~2.5%
In the methanol solution environment of sodium hydroxide, heating reflux reaction；
Preferably, in the methanol solution environment containing 2~2.5% sodium hydroxides, heating reflux reaction.
7. discrimination method according to claim 1, which is characterized in that the method for the pre-column derivatization are as follows: boron trifluoride
Methyl esterization, preferably are as follows:
Containing heating reflux reaction in 10~15% boron trifluoride methanol solution；
Preferably, containing heating reflux reaction in 10~14% boron trifluoride methanol solution；
Preferably, after the pre-column derivatization and before the detection further include: extracted with normal heptane.
8. discrimination method according to claim 5, which is characterized in that solvent used is positive heptan when detecting the reference substance
Alkane.
9. the discrimination method of polyoxyethylene sorbitan monoleate in Shenmai injection, which is characterized in that described in any item using claim 1-8
Discrimination method identifies the quality of polyoxyethylene sorbitan monoleate in the Shenmai injection.
10. discrimination method according to claim 9, which is characterized in that heating time in the step A be 10min with
On；
Preferably, 75 DEG C are cooled to described in the step A the above are be cooled to 75~95 DEG C；
Preferably, the time of standing described in the step A is within 0.5 hour.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811051028.2A CN109187829B (en) | 2018-09-10 | 2018-09-10 | Method for identifying polysorbate 80 in injection and Shenmai injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811051028.2A CN109187829B (en) | 2018-09-10 | 2018-09-10 | Method for identifying polysorbate 80 in injection and Shenmai injection |
Publications (2)
| Publication Number | Publication Date |
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| CN109187829A true CN109187829A (en) | 2019-01-11 |
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| CN113092603A (en) * | 2021-03-17 | 2021-07-09 | 中国药科大学 | Method for measuring polysorbate 80 content in Shenmai injection |
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