CN108956803A - A kind of method of quality control of Cefixime - Google Patents
A kind of method of quality control of Cefixime Download PDFInfo
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- CN108956803A CN108956803A CN201810509889.4A CN201810509889A CN108956803A CN 108956803 A CN108956803 A CN 108956803A CN 201810509889 A CN201810509889 A CN 201810509889A CN 108956803 A CN108956803 A CN 108956803A
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- cefixime
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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
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Abstract
The invention discloses a kind of method of quality control of Cefixime, use octadecylsilane chemically bonded silica for the chromatographic column of filler, its testing conditions is as follows: mobile phase: A phase: tetrabutylammonium hydroxide aqueous solution (pH 6.5): acetonitrile=50:50, B phase: tetrabutylammonium hydroxide aqueous solution (pH 6.5): acetonitrile=85:15, column temperature: 0-50 DEG C, sample volume: 5-25 μ L, sample introduction concentration: 0.0005-2mg/mL, flow velocity: 0.8-1.5mL/min, Detection wavelength: 254nm.Method of the invention may be implemented the unknown impuritie that the prior art can not be detected efficiently separate and quantitative detection, and detection efficiency and accuracy in detection are above the prior art, this method universality with higher can be widely applied to the quality testing of the Cefixime bulk pharmaceutical chemicals and its corresponding preparation of separate sources.
Description
Technical field
The invention belongs to Pharmaceutical Analysis fields, specifically control about the quality of a kind of Cefixime bulk pharmaceutical chemicals and preparation
Method.
Background technique
Cefixime (Cefixime, CAS:79350-37-1) takes orally cephalosporin analog antibiotic for the third generation, clinically leads
It is used to treat pharyngitis caused by sensitive bacteria, tonsillitis, acute bronchitis acute attack, tympanitis, urinary tract infection etc..Head
Spore gram oxime has the characteristics that spectrum, efficient, long half time, structural formula are as follows:
It is to need to give strictly in antibiotic clinical use using anaphylactic type antibiotic allergy as the adverse drug reaction of representative
The phenomenon that controlling and avoiding, and related substance contained in bulk pharmaceutical chemicals is a series of important root for causing adverse drug reactions
One of.Therefore, most important for the analysis and research in relation to substance in bulk pharmaceutical chemicals and corresponding preparation.
Different preparation process routes, corresponding impurity feelings may be used based on the different Cefixime bulk pharmaceutical chemicals in source
Condition has differences, and existing method needs to realize efficiently separating and quantitatively examining to the plurality of impurities including unknown impuritie
It surveys, and then the quality control to Cefixime bulk pharmaceutical chemicals and corresponding preparation may be implemented.
Specifically, United States Pharmacopeia (USP 41), Chinese Pharmacopoeia (2015 editions), European Pharmacopoeia (EP 9.0) and Japanese officina
Fang Jun describes the raw material of Cefixime and the analysis method of preparation, and it is water-soluble to be all made of acetonitrile-tetrabutylammonium hydroxide buffering
Liquid system is as mobile phase, and the method eluted using fixed proportion mobile phase, elution time is in 45min or so (3 times of cephalos gram
Oxime retention time), the conventional quantitative detection in relation to substance may be implemented in this method, but the detection of special unknown impuritie is imitated
Fruit is bad.
" Pharmaceutical Analysis magazine ", side are of heap of stone etc., and 2010,30 (5), P872 discloses a kind of acetonitrile assisted electrospray LC-MS/MS
Method analyzes the method in relation to substance in Cefixime, and this method is stream with 1% aqueous formic acid-acetonitrile (90:10A)-acetonitrile (B)
Dynamic phase is separated, elution time 40min, the party using the method realization effective component of gradient elution and the elution in relation to substance
Method may be implemented to 21 common quantitative detections in relation to substance, but for special unknown impuritie, because of elution time
It is shorter, and make the separating degree of partial impurities and/or peak type bad, or even the situation for thering is inspection not measure, comprehensive detection
Effect is still bad.
" chromatography ", Zhang Xiuyao etc., 2014,32 (7), P693 are disclosed in a kind of ultra performance liquid chromatography general formula measurement milk
Beta-lactam antibiotic and its remaining method of metabolite, this method, as mobile phase, are adopted using aqueous solution-acetonitrile system
With the method for gradient elution, elution time 10min, still, this method only realize point of each antibiotic and its metabolite peak
From can not achieve the detection in relation to substance lesser to content.
In summary, the method for quality control of a kind of Cefixime bulk pharmaceutical chemicals and its preparation is found, to realize to including not
Know that efficiently separating with quantitative detection for the plurality of impurities including impurity is prior art open question.
Summary of the invention
The purpose of the present invention is to overcome the shortcomings of the existing technology, provides a kind of method of quality control of Cefixime, should
Method, which can detecte the prior art, cannot achieve the unknown impuritie of qualitative/quantitative detection, and realization is efficiently separated to more polymictic
And quantitative detection, and detection efficiency and accuracy in detection are above the prior art, can be widely applied to the cephalo of separate sources
The quality testing of gram oxime bulk pharmaceutical chemicals and its corresponding preparation.
Above-mentioned purpose of the invention is achieved by the following technical programs:
In the method for quality control of Cefixime of the invention, the method for quality control of the Cefixime is using efficient
Liquid phase method uses octadecylsilane chemically bonded silica for the chromatographic column of filler, and testing conditions are as follows:
Mobile phase:
A phase: tetrabutylammonium hydroxide aqueous solution (pH 6.5): acetonitrile=50:50
B phase: tetrabutylammonium hydroxide aqueous solution (pH 6.5): acetonitrile=85:15
Column temperature: 0~50 DEG C
Sample volume: 5~25 μ L
Sample introduction concentration: 0.0005~2mg/mL
Flow velocity: 0.8~1.5mL/min
Detection wavelength: 254nm
The method of quality control of the Cefixime comprises the steps of:
1) sample solution, is prepared；
2), sample introduction；
3) it, is eluted using linear gradient elution method, gradient is provided that
| Stage | VA phase:VB phase | Elution time |
| 0 | 20:80~25:75 | 0min |
| 1 | 20:80~25:75 | 35~45min |
| 2 | 50:50~85:15 | 15~35min |
| 3 | 20:80~25:75 | 2~10min |
| 4 | 20:80~25:75 | 10~20min |
。
Specifically, the configuration method of the tetrabutylammonium hydroxide aqueous solution (pH 6.5) in the mobile phase are as follows: take 10%
Tetrabutylammonium hydroxide solution 25mL, adds purified water to be diluted to 1000mL, shakes up, with 1.5mol/L phosphoric acid solution adjust pH to
6.5 to obtain the final product；Test sample the preparation method comprises the following steps: taking Cefixime 50mg specification dispersible tablet 5, precise weighing is placed in 250mL appearance
Measuring bottle, addition pH7.0 phosphate buffer to about 2/3 scale, ultrasonic 30min, addition 7.0 phosphate buffer of pH to scale,
It filters to obtain the final product.7.0 phosphate buffer of pH the preparation method comprises the following steps: taking potassium dihydrogen phosphate 6.805g and sodium hydroxide
0.94g, it is accurately weighed, add appropriate amount of water to dissolve, be diluted with water to 1000ml, first adjusts pH to about with saturation sodium hydroxide solution
PH6.9, then pH value is adjusted to 7.0 with the sodium hydroxide solution of l mol/L, it deaerates before use.
The column temperature of the Cefixime method of quality control needs to control between 0 to 50 DEG C, and too low column temperature can be serious
Column effect is influenced, and excessively high column temperature can then damage chromatographic column；Preferably, when the column temperature of the method for quality control of the Cefixime
When being 40 DEG C, the appearance time and peak type peak of each ingredient are best, and detection effect is best.
The sample volume of the Cefixime method of quality control needs to control in 5~25 μ L, and sample introduction concentration needs to control
0.0005~2mg/mL, it is linear between concentration and peak area at this time；Preferably, when the Cefixime quality controlling party
The sample volume of method is 20 μ L, and when sample introduction concentration is 0.8~1.2mg/mL, the sample size of unit detection can play to the greatest extent
The effect for flowing elution, be advantageously implemented it is each separated at swarming, and testing result is the most accurate.
The flow velocity of mobile phase is one of the key problem in technology for realizing detection effect, tool in the Cefixime method of quality control
Body, the flow velocity of mobile phase is excessively high to accelerate elution speed, shorten appearance time, and be unfavorable for realization separating effect, and mistake
Low flow velocity can then reduce elution speed, can also widen each component peak width while appearance time delay, equally be unfavorable for reality
Existing separating effect, also reduces detection efficiency；More specifically, when the flow control of mobile phase is in 0.8~1.5mL/min, institute
The method of stating takes into account detection efficiency and separating degree, is advantageously implemented optimum detection effect, when flow velocity is 1.2mL/min, detection effect
Fruit is best.
The setting of gradient elution is to realize that the important technology of detection effect is crucial in the Cefixime method of quality control.
Specifically, it was discovered by researchers that each impurity peaks separating degree before principal component peak is preferable, and the impurity peaks after principal component peak then because
Polarity is similar and corresponds to appearance time approximation, in the presence of the phenomenon being overlapped, cladding or peak type are bad between each peak, is unfavorable for unknown
The qualitative and quantitative detection of impurity, thus main peak slightly before or later increase by one section of gradient, retained more by force with quickly eluting
Impurity, and guarantee that the peak type of related eluting peak and the separating degree at each peak, the gradient elution are provided that
| Stage | VA phase:VB phase | Elution time |
| 0 | 20:80~25:75 | 0min |
| 1 | 20:80~25:75 | 35~45min |
| 2 | 50:50~85:15 | 15~35min |
| 3 | 20:80~25:75 | 2~10min |
| 4 | 20:80~25:75 | 10~20min |
In above-mentioned gradient elution setting, the elution time refers to the lasting duration of the stepwise elution, the ratio of mobile phase
Example (VA phase:VB phase) refer to reach the elution time terminal when mobile phase ratio, wherein the stage 0 refer to mobile phase original ratio,
That is: in the elution time section, the ratio of mobile phase is faded to the end point values of this period by the end point values of previous period, such as
Nothing is refered in particular to, and the explanation of all gradients settings conforms to this in the present invention.Preferably, the ratio of mobile phase is in elution time
At the uniform velocity change.
More specifically, the stage 2 of above-mentioned gradient elution setting can be further refined as the stage 2,3,4, be conducive to more excellent
Separating effect, it is as follows:
| Stage | VA phase:VB phase | Elution time |
| 0 | 20:80~25:75 | 0min |
| 1 | 20:80~25:75 | 35~45min |
| 2 | 50:50~70:30 | 5~15min |
| 3 | 70:30~75:25 | 5~10min |
| 4 | 75:25~85:15 | 5~10min |
| 5 | 20:80~25:75 | 2~10min |
| 6 | 20:80~25:75 | 10~20min |
The method of quality control of the preferred Cefixime of of the invention one, wherein gradient elution is provided that
| Stage | VA phase:VB phase | Elution time |
| 0 | 23:77 | 0min |
| 1 | 23:77 | 40min |
| 2 | 60:40 | 9min |
| 3 | 72:28 | 6min |
| 4 | 80:20 | 7min |
| 5 | 23:77 | 4min |
| 6 | 23:77 | 14min |
The method of quality control of the preferred Cefixime of of the invention one, wherein gradient elution is provided that
| Stage | VA phase:VB phase | Elution time |
| 0 | 25:75 | 0min |
| 1 | 25:75 | 45min |
| 2 | 55:45 | 12min |
| 3 | 70:30 | 7min |
| 4 | 85:15 | 4min |
| 5 | 25:75 | 2min |
| 6 | 25:75 | 10min |
Chromatographic column can use being bonded with octadecylsilane for different brands in the Cefixime method of quality control
Silica gel is the chromatographic column of filler, specifically, the chromatographic column can be Agilent ZORBAX SB-C18, Waters
Xbridge shield RP18、Agela Luna C18(2) etc..
The method of quality control of the Cefixime has preferable universality, can be adapted for various impurity situation raw materials
In the quality control of medicine and its corresponding preparation.
Efficiently separating and quantitatively examining for the unknown impuritie that can not be detected to the prior art may be implemented in method of the invention
It surveys, and detection efficiency and accuracy in detection are above the prior art, this method universality with higher can be widely applied to
The quality testing of the Cefixime bulk pharmaceutical chemicals of separate sources and its corresponding preparation.
Detailed description of the invention
Fig. 1 is 1 gained HPLC spectrogram of embodiment.
Fig. 2 is 2 gained HPLC spectrogram of embodiment.
Fig. 3 is 1 gained HPLC spectrogram of comparative example.
Fig. 4 is 2 gained HPLC spectrogram of comparative example.
Specific embodiment
Below with reference to embodiment and attached drawing, the present invention is described in further detail, but the embodiment invented is not limited to
This.
Embodiment 1
Chromatographic column: Agilent ZORBAX SB-C18,250 × 4.6mm, 5 μm
Mobile phase:
A phase: tetrabutylammonium hydroxide aqueous solution: acetonitrile=50:50
B phase: tetrabutylammonium hydroxide aqueous solution: acetonitrile=85:15
Column temperature: 40 DEG C
Sample volume: 20 μ L
Sample introduction concentration 1mg/mL
Flow velocity: 1.2mL/min
Detection wavelength: 254nm
The method of quality control of the Cefixime comprises the steps of:
1, solution is prepared；
10% tetrabutylammonium hydroxide solution 25mL is taken, adds purified water to be diluted to 1000mL, shakes up, with 1.5mol/L phosphoric acid
Solution adjusts pH to 6.5 and obtains tetrabutylammonium hydroxide aqueous solution；By the tetrabutylammonium hydroxide aqueous solution and acetonitrile of corresponding amount
Mixing, respectively obtains A phase and B phase；
It takes cefixime dispersible tablet 5 (50mg specification), precise weighing, is placed in 250mL volumetric flask, 7.0 phosphoric acid of pH is added
Salt buffer is to about 2/3 scale, ultrasonic 30min, and 7.0 phosphate buffer of pH is added to scale；It filters up to test sample；
2, sample introduction；
3, using following gradient elution:
| Stage | VA phase:VB phase | Elution time |
| 0 | 23:77 | 0min |
| 1 | 23:77 | 40min |
| 2 | 60:40 | 9min |
| 3 | 72:28 | 6min |
| 4 | 80:20 | 7min |
| 5 | 23:77 | 4min |
| 6 | 23:77 | 14min |
Gained HPLC spectrogram is as shown in Figure 1, it can be seen that altogether detect 6 impurity, impurity peaks peak type is good, main peak with it is adjacent
The separating degree at peak is that 4.02, wherein unknown impuritie 1 (t=57.281min) and unknown impuritie 2 (t=59.326min) are new discovery
Two impurity peaks, the qualitative detection and quantitative detection to unknown impuritie 1 and unknown impuritie 2 may be implemented using this method.
Inspection that is subsequent that bulk pharmaceutical chemicals and other specification cefixime preparations is used to configure test sample for test object, obtaining
It surveys result and embodiment 1 is almost the same.
Embodiment 2
Chromatographic column: Agilent ZORBAX SB-C18,250 × 4.6mm, 5 μm
Mobile phase:
A phase: tetrabutylammonium hydroxide aqueous solution: acetonitrile=50:50
B phase: tetrabutylammonium hydroxide aqueous solution: acetonitrile=85:15
Column temperature: 40 DEG C
Sample volume: 20 μ L
Sample introduction concentration 1mg/mL
Flow velocity: 1.2mL/min
Detection wavelength: 254nm
The method of quality control of the Cefixime comprises the steps of:
1, solution is prepared；
10% tetrabutylammonium hydroxide solution 25mL is taken, adds purified water to be diluted to 1000mL, shakes up, with 1.5mol/L phosphoric acid
Solution adjusts pH to 6.5 and obtains tetrabutylammonium hydroxide aqueous solution；By the tetrabutylammonium hydroxide aqueous solution and acetonitrile of corresponding amount
Mixing, respectively obtains A phase and B phase；
It takes cefixime dispersible tablet 5 (50mg specification), precise weighing, is placed in 250mL volumetric flask, 7.0 phosphoric acid of pH is added
Salt buffer is to about 2/3 scale, ultrasonic 30min, and 7.0 phosphate buffer of pH is added to scale；It filters up to test sample；
2, sample introduction；
3, using following gradient elution:
Gained HPLC spectrogram is as shown in Figure 2, it can be seen that altogether detect 6 impurity, impurity peaks peak type is good, main peak with it is adjacent
The separating degree at peak is that 2.73, wherein unknown impuritie 1 (t=61.600min) and unknown impuritie 2 (t=63.083min) are new discovery
Two impurity peaks, the qualitative detection and quantitative detection to unknown impuritie 1 and unknown impuritie 2 may be implemented using this method.
Comparative example 1
The Cefixime detection method detection recorded using European Pharmacopoeia (EP 9.0), specific as follows:
Chromatographic column: Agilent ZORBAX SB-C18,250 × 4.6mm, 5 μm
Mobile phase:
A phase: 0.01mol/L tetrabutylammonium hydroxide solution (pH6.5)
B phase: acetonitrile
VA phase:VB phase=3:1
Column temperature: 40 DEG C
Sample volume: 10 μ L
Flow velocity: 1.0mL/min
Detection wavelength: 254nm
The method of quality control of the Cefixime comprises the steps of:
1, solution is prepared；
The 0.01mol/L tetrabutylammonium hydroxide aqueous solution adjusting pH value of corresponding amount to 6.5 is obtained into A phase, by A phase and B
The mutually ratio mixing of 3:1 by volume, obtains mobile phase；
It takes cefixime dispersible tablet 5 (50mg specification), precise weighing, is placed in 250mL volumetric flask, 7.0 phosphoric acid of pH is added
Salt buffer is to about 2/3 scale, ultrasonic 30min, and 7.0 phosphate buffer of pH is added to scale；It filters up to test sample；
2, sample introduction；
3, using fixed mobile phase elution；
Gained HPLC spectrogram is as shown in Figure 3, it can be seen that do not found in spectrogram as shown in Figure 1, Figure 2 shown in unknown impuritie
1 and 2 peak of unknown impuritie, and main peak and adjacent peak separating degree are 2.07, and opposite embodiment 1 and embodiment 2 are smaller, it is known that use
This method cannot achieve the qualitative detection and quantitative detection to unknown impuritie 1 and unknown impuritie 2, and the separating degree of this method is also too late
Method of the invention.
The subsequent analysis method recorded using United States Pharmacopeia (USP 41), Chinese Pharmacopoeia (2015 editions) and Pharmacopeia of Japan
It repeats to obtain the testing result almost the same with Fig. 3 in experiment.
Comparative example 2
Reference literature: " Pharmaceutical Analysis magazine ", side are of heap of stone etc., 2010,30 (5), Cefixime detection method disclosed in P872
Detection, specific as follows:
Chromatographic column: Agilent ZORBAX SB-C18,250 × 4.6mm, 5 μm
Mobile phase:
A phase: 1% formic acid solution: acetonitrile=90:10
B phase: acetonitrile
Column temperature: 35 DEG C
Sample volume: 20 μ L
Flow velocity 1.0mL/min
PDA scanning wavelength range: 200~600nm
1, solution is prepared；
Formic acid 10g is taken, purified water is added to be diluted to 1000mL, is shaken up, 1% formic acid solution is obtained；By 1% formic acid of corresponding amount
Solution is mixed with acetonitrile, obtains A phase；Acetonitrile is taken, B phase is obtained.
It takes cefixime dispersible tablet 5 (50mg specification), precise weighing, is placed in 250mL volumetric flask, 7.0 phosphoric acid of pH is added
Salt buffer is to about 2/3 scale, ultrasonic 30min, and 7.0 phosphate buffer of pH is added to scale；It filters up to test sample；
2, sample introduction；
3, elution is arranged using the gradient that document is recorded:
Gained HPLC spectrogram is as shown in Figure 4, it can be seen that also do not found in spectrogram as shown in Figure 1, Figure 2 shown in it is unknown miscellaneous
2 peak of matter 1 and unknown impuritie.It knows to cannot achieve the qualitative detection to unknown impuritie 1 and unknown impuritie 2 using this method and quantify
Detection
Known to comprehensive: using embodiment 1, the method for embodiment 2, can detecte more unknown impurities, and realize phase
Efficiently separating for substance is closed, and qualitative detection and quantitative detection can be further realized, is conducive to Cefixime bulk pharmaceutical chemicals and system
The quality of agent controls, and has compared with detection method disclosed in the prior art (such as: comparative example 1, comparative example 2) higher general
Adaptive.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, other any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present invention,
It should be equivalent substitute mode, be included within the scope of the present invention.
Claims (10)
1. a kind of method of quality control of Cefixime, which is characterized in that the method for quality control of the Cefixime is using high
Liquid phase method is imitated, uses octadecylsilane chemically bonded silica for the chromatographic column of filler, testing conditions are as follows:
Mobile phase:
A phase: tetrabutylammonium hydroxide aqueous solution (pH6.5): acetonitrile=50:50
B phase: tetrabutylammonium hydroxide aqueous solution (pH6.5): acetonitrile=85:15
Column temperature: 0~50 DEG C
Sample volume: 5~25 μ L
Sample introduction concentration: 0.0005~2mg/mL
Flow velocity: 0.8~1.5mL/min
Detection wavelength: 254nm
The method of quality control of the Cefixime comprises the steps of:
1) sample solution, is prepared；
2), sample introduction；
3) it, is eluted using linear gradient elution method, gradient is provided that
2. the method for quality control of Cefixime according to claim 1, it is characterised in that four fourths in the mobile phase
The configuration method of base ammonium hydroxide aqueous solution (pH6.5) are as follows: take 10 (quality) % tetrabutylammonium hydroxide solution 25mL, add purifying
Water is diluted to 1000mL, shakes up, and adjusts pH to 6.5 with 1.5mol/L phosphoric acid solution to obtain the final product；Test sample the preparation method comprises the following steps: taking
Cefixime 50mg specification dispersible tablet 5, precise weighing is placed in 250mL volumetric flask, and pH7.0 phosphate buffer is added to about
2/3 scale, ultrasonic 30min are added pH7.0 phosphate buffer to scale, filter to obtain the final product.
3. the method for quality control of Cefixime according to claim 1, it is characterised in that the column temperature is 40 DEG C, into
Sample amount is 20 μ L, flow velocity 1.2mL/min.
4. the method for quality control of Cefixime according to claim 1, it is characterised in that the gradient elution setting
It is as follows:
5. the method for quality control of Cefixime according to claim 1, it is characterised in that the gradient elution setting
Are as follows:
6. the method for quality control of Cefixime according to claim 1, it is characterised in that the gradient elution setting
Are as follows:
7. the method for quality control of Cefixime according to claim 1, it is characterised in that the chromatographic column is
Agilent ZORBAX SB-C18、Waters Xbridge shield RP18、Agela Luna C18(2) any one in
Kind.
8. the method for quality control of Cefixime described in one of -9 according to claim 1, it is characterised in that the mobile phase
Ratio at the uniform velocity changes in elution time.
9. a kind of method of quality control of Cefixime, it is characterised in that testing conditions are as follows:
Chromatographic column: Agilent ZORBAX SB-C18,250 × 4.6mm, 5 μm
Mobile phase:
A phase: tetrabutylammonium hydroxide aqueous solution: acetonitrile=50:50
B phase: tetrabutylammonium hydroxide aqueous solution: acetonitrile=85:15
Column temperature: 40 DEG C
Sample volume: 20 μ L
Flow velocity: 1.2mL/min
Detection wavelength: 254nm
The method of quality control of the Cefixime comprises the steps of:
1, solution is prepared；
10% tetrabutylammonium hydroxide solution 25mL is taken, adds purified water to be diluted to 1000mL, shakes up, with 1.5mol/L phosphoric acid solution
It adjusts pH to 6.5 and obtains tetrabutylammonium hydroxide aqueous solution；The tetrabutylammonium hydroxide aqueous solution of corresponding amount is mixed with acetonitrile,
Respectively obtain A phase and B phase；
Cefixime dispersible tablet 5 are taken, 50mg specification, precise weighing is placed in 250mL volumetric flask, and it is slow that 7.0 phosphate of pH is added
Fliud flushing is to about 2/3 scale, ultrasonic 30min, and 7.0 phosphate buffer of pH is added to scale；It filters up to test sample；
2, sample introduction；
3, using following gradient elution:
10. a kind of method of quality control of Cefixime, it is characterised in that testing conditions are as follows:
Chromatographic column: Agilent ZORBAX SB-C18,250 × 4.6mm, 5 μm
Mobile phase:
A phase: tetrabutylammonium hydroxide aqueous solution: acetonitrile=50:50
B phase: tetrabutylammonium hydroxide aqueous solution: acetonitrile=85:15
Column temperature: 40 DEG C
Sample volume: 20 μ L
Flow velocity: 1.2mL/min
Detection wavelength: 254nm
The method of quality control of the Cefixime comprises the steps of:
1, solution is prepared；
10% tetrabutylammonium hydroxide solution 25mL is taken, adds purified water to be diluted to 1000mL, shakes up, with 1.5mol/L phosphoric acid solution
It adjusts pH to 6.5 and obtains tetrabutylammonium hydroxide aqueous solution；The tetrabutylammonium hydroxide aqueous solution of corresponding amount is mixed with acetonitrile,
Respectively obtain A phase and B phase；
Cefixime dispersible tablet 5 are taken, 50mg specification, precise weighing is placed in 250mL volumetric flask, and it is slow that 7.0 phosphate of pH is added
Fliud flushing is to about 2/3 scale, ultrasonic 30min, and 7.0 phosphate buffer of pH is added to scale；It filters up to test sample；
2, sample introduction；
3, using following gradient elution:
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| CN111323529A (en) * | 2020-04-23 | 2020-06-23 | 广东华南药业集团有限公司 | Method for separating and measuring dextromethorphan and levomethorphan by liquid chromatography |
| CN111487354A (en) * | 2020-04-27 | 2020-08-04 | 广州白云山医药集团股份有限公司白云山制药总厂 | Method for detecting cefixime related impurities |
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| CN111323529A (en) * | 2020-04-23 | 2020-06-23 | 广东华南药业集团有限公司 | Method for separating and measuring dextromethorphan and levomethorphan by liquid chromatography |
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| CN111487354A (en) * | 2020-04-27 | 2020-08-04 | 广州白云山医药集团股份有限公司白云山制药总厂 | Method for detecting cefixime related impurities |
| CN111551654A (en) * | 2020-05-07 | 2020-08-18 | 广州白云山医药集团股份有限公司白云山制药总厂 | Method for detecting cefixime polymer impurities |
| CN111551654B (en) * | 2020-05-07 | 2022-04-22 | 广州白云山医药集团股份有限公司白云山制药总厂 | Method for detecting cefixime polymer impurities |
| CN114609296A (en) * | 2022-03-29 | 2022-06-10 | 水羊化妆品制造有限公司 | Detection method of enzymolysis hyaluronic acid oligosaccharide mixture |
| CN114609296B (en) * | 2022-03-29 | 2024-01-05 | 水羊化妆品制造有限公司 | Detection method for enzymatic hydrolysis hyaluronic acid oligosaccharide mixture |
| CN115326950A (en) * | 2022-07-27 | 2022-11-11 | 广州白云山医药集团股份有限公司白云山制药总厂 | Method for detecting dissolution rate of cefixime |
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