CN109596725A - A kind of phthalic anhydride and its detection method in relation to substance - Google Patents
A kind of phthalic anhydride and its detection method in relation to substance Download PDFInfo
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- CN109596725A CN109596725A CN201811396875.2A CN201811396875A CN109596725A CN 109596725 A CN109596725 A CN 109596725A CN 201811396875 A CN201811396875 A CN 201811396875A CN 109596725 A CN109596725 A CN 109596725A
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- mobile phase
- phthalic anhydride
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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
Abstract
The present invention relates to chemicals analysis method technical field, in particular to a kind of phthalic anhydride and its detection method in relation to substance.It is characterized by: carrying out gradient elution on high performance liquid chromatograph, the phthalic anhydride appearance in the form of phthalic acid under this condition, its chromatographic condition includes: that chromatographic column is octyl silane group silica gel chromatographic column, using potassium phosphate buffer as mobile phase A, acetonitrile is Mobile phase B, and Detection wavelength is 225~235nm, 30-37 DEG C of column temperature, flow velocity: 0.8-1.2mL/min carries out gradient elution；Wherein mobile phase A preparation method is: taking potassium dihydrogen phosphate 0.61g, 1000mL is dissolved and be diluted to water, with phosphorus acid for adjusting pH value to 2.2-2.6.The present invention can efficiently separate phthalic anhydride and its related substance, and separating degree is good, so as to effectively control the quality of phthalic anhydride.
Description
(1) technical field
The present invention relates to chemicals analysis method technical field, in particular to a kind of phthalic anhydride and its detection side in relation to substance
Method.
(2) background technique
It is well known that influence of the pharmaceutical purity to patient is very big.Injecting drug impurity is to cause adverse drug reaction (such as
Allergy, drug fever etc.) the main reason for.Oral drugs are impure, can increase the incidence of adverse reaction, such as Nausea and vomiting, abdomen
Bitterly, diarrhea etc..Meanwhile what may be influenced is the absorption of drug, to influence curative effect of medication.Therefore, the detection side of pharmaceutical purity
Method is just particularly important, and refers to the starting material brought into production of raw medicine in relation to substance (Telated substances)
The substances such as material, reagent, intermediate, by-product, it is also possible to which the degradation that preparation generates in production, storage and transportational process produces
The special impurities such as object, polymer or crystal transfer.Type and the close phase of synthetic route and production technology of drug in relation to substance
It closes, different synthetic route and production technology, the impurity spectrum of drug can also change, and therefore, it is necessary to according to different synthesis
Route and production technology establish suitable analysis method, reach the detection and monitoring accurate and effective in relation to substance to phthalic anhydride.
Currently, for pharmaceutical purity detection method also there are many, wherein the detection of related substance is control drug quality
Important indicator.Phthalic anhydride (Phthalic anhydride), the entitled phthalic anhydride of chemistry, molecular formula C8H4O3, molecular weight
It is 148.11, No. CAS is 85-44-9, and structural formula is as follows:
Phthalic anhydride is one of the main starting material for synthesizing fluorescein sodium, in order to guarantee the safe and effective of drug, is needed to drug
Related substance is studied, detected and is monitored.Phthalic anhydride national standard (GB/T 15336-2013) regulation is surveyed with GC method
Fixed related substance.
Main problem existing for the technical solution be its related substance method can not to known impurities (terephthalic acid (TPA) and
Phthalic acid) it is effectively separated.
(3) summary of the invention
In order to compensate for the shortcomings of the prior art, the present invention provides a kind of phthalic anhydride and its in relation to the detection method of substance.
The present invention is achieved through the following technical solutions:
A kind of phthalic anhydride and its detection method in relation to substance, it is characterised in that: gradient elution is carried out on high performance liquid chromatograph,
The appearance in the form of phthalic acid, chromatographic condition include: that chromatographic column is octyl silane group silicon to phthalic anhydride under this condition
Glue chromatographic column, using potassium phosphate buffer as mobile phase A, acetonitrile is Mobile phase B, and Detection wavelength is 225~235nm, column temperature
30-37 DEG C, flow velocity: 0.8-1.2mL/min carries out gradient elution；Wherein mobile phase A preparation method is: taking potassium dihydrogen phosphate
0.61g dissolves with water and is diluted to 1000mL, with phosphorus acid for adjusting pH value to 2.2-2.6.
Further, the process of the gradient elution are as follows: in 0~30min, the volume ratio 85:15 of mobile phase A and Mobile phase B；
In 30~50min, the volume ratio of mobile phase A and Mobile phase B is from 85:15 at the uniform velocity gradual change to 20:80；In 50~51min, flowing
The volume ratio of phase A and Mobile phase B is from 20:80 at the uniform velocity gradual change to 85:15；In 51~70min, the volume of mobile phase A and Mobile phase B
Than for 85:15.
Wherein, in mobile phase A, the concentration of potassium dihydrogen phosphate is 0.55g/L~0.67g/L.
More excellent, the concentration of the potassium dihydrogen phosphate is 0.61g/L.
Wherein, in 0~30min, the volume ratio of mobile phase A and Mobile phase B is 84:16~87:13.
More excellent, the volume ratio of the mobile phase A and Mobile phase B is 85:15.
Wherein, the length of the chromatographic column is 250mm, and diameter 4.6mm, packing material size is 5 μm.
Wherein, the Detection wavelength is 230nm.
Wherein, the column temperature is 35 DEG C.
Wherein, the flow velocity is 1.0mL/min.
In the present invention, the related substance is
(terephthalic acid (TPA), impurity A)(M-phthalic acid, impurity B
The beneficial effects of the present invention are:
The present invention can efficiently separate phthalic anhydride and its related substance, and separating degree is good, so as to effectively control phthalic anhydride
Quality.Method of the invention can it is simple, fast and accurately separation detection goes out phthalic anhydride and its in relation to substance and associated
Potential impurity, and specificity is strong, high sensitivity, stability are good, favorable reproducibility, precision are high, peak shape is good, can be used for practical life
Effective control in production.
(4) Detailed description of the invention
The present invention will be further described below with reference to the drawings.
Fig. 1 is the chromatogram of 1 blank solution of embodiment.
Fig. 2 is the chromatogram of the mixed reference substance solution of embodiment 1.
Fig. 3 is the chromatogram of the phthalic anhydride test sample of embodiment 1.
Fig. 4 is the chromatogram of the mixed reference substance solution of embodiment 2.
Fig. 5 is the chromatogram of the phthalic anhydride test solution of embodiment 2.
Fig. 6 is the chromatogram of the mixed reference substance solution of embodiment 3.
Fig. 7 is the chromatogram of the phthalic anhydride test solution of embodiment 3.
Fig. 8 is the chromatogram of the mixed reference substance solution of embodiment 4.
Fig. 9 is the chromatogram of the phthalic anhydride test solution of embodiment 4.
Figure 10 is the mixed reference substance solution chromatogram of embodiment 5.
Figure 11 is the chromatogram of the phthalic anhydride test solution of embodiment 5.
(5) specific embodiment
Embodiment 1
(1) testing conditions
Instrument: waters e2695 high performance liquid chromatograph, 2998PDA detector, Detection wavelength: 280nm；
Chromatographic column: waters Symmetry C8(250mm × 4.6mm, 5 μm) chromatographic column；
Solvent: mobile phase A: potassium phosphate buffer (takes 0.61g potassium dihydrogen phosphate, water 1000ml is added to make to dissolve, with phosphoric acid tune
PH value is saved to 2.40)；Mobile phase B: acetonitrile；Mobile phase A and Mobile phase B volume ratio are as follows: 85:15；
Flow velocity: 1.0mL/min
Column temperature: 35 DEG C；
Sample volume: 20 μ L；
Linear gradient elution is carried out by table 1.
Table 1
(2) detecting step
The preparation of blank solution: taking dimethyl sulfoxide 5ml, sets in 100ml measuring bottle, adds 15% acetonitrile water to be diluted to scale, shakes up,
As blank solution.
The preparation of mixed reference substance solution: taking impurity A and impurity B each appropriate respectively, accurately weighed, and dimethyl sulfoxide is added to shake
Shaking makes to dissolve, and is diluted to the solution that every 1ml contains 0.5 μ g with 15% acetonitrile water, as mixed reference substance solution.
The preparation of test solution: taking phthalic anhydride test sample about 50mg, accurately weighed, sets in 100ml measuring bottle, adds 5ml diformazan
Base sulfoxide makes to dissolve, and is diluted to scale with 15% acetonitrile water, shakes up, as test solution.
It is accurate respectively to measure blank solution, mixed reference substance solution and each 20 μ L of test solution, liquid chromatograph is injected,
Chromatogram is recorded, sees Fig. 1, Fig. 2, Fig. 3；The result shows that: in Fig. 2, each peak is followed successively by impurity A (9.629min), phthalic anhydride
(11.584min), impurity B (13.094min).
Embodiment 2
According to the similar detection method of embodiment 1, wherein potassium dihydrogen phosphate concentration replaces with 0.55g/L.It mixes control
The map of product is shown in Fig. 4, the chromatogram of test sample is shown in Fig. 5.
Embodiment 3
According to the similar detection method of embodiment 1, wherein potassium dihydrogen phosphate concentration replaces with 0.67g/L.It mixes control
The chromatogram of product is shown in Fig. 6, the chromatogram of test sample is shown in Fig. 7.
Embodiment 4
According to the similar detection method of embodiment 1, wherein the volume ratio of mobile phase A and Mobile phase B replaces in 0~30min
84:16.Its map for mixing reference substance is shown in Fig. 8, the map of test sample is shown in Fig. 9.
Embodiment 5
According to the similar detection method of embodiment 1, wherein the volume ratio of mobile phase A and Mobile phase B replaces in 0~30min
87:13.The map of its mixed reference substance solution is shown in Figure 10, the chromatogram of test sample is shown in Figure 11.
The above test explanation: this method can be with the related substance in quantitative detection phthalic anhydride, to mention to the control of product quality
The better foundation supplied.
Reagent used in the present invention is available on the market.
The foregoing is only a preferred embodiment of the present invention, but scope of protection of the present invention is not limited thereto,
Anyone skilled in the art in the technical scope disclosed by the present invention, according to the technique and scheme of the present invention and its
Inventive concept is subject to equivalent substitution or change, should be covered by the protection scope of the present invention.
Claims (9)
1. a kind of phthalic anhydride and its detection method in relation to substance, it is characterised in that: carry out gradient on high performance liquid chromatograph and wash
De-, chromatographic condition includes: that chromatographic column is octyl silane group silica gel chromatographic column, using potassium phosphate buffer as mobile phase
A, acetonitrile are Mobile phase B, and Detection wavelength is 225~235nm, and 30-37 DEG C of column temperature, flow velocity: 0.8-1.2mL/min carries out gradient
Elution；Wherein mobile phase A preparation method is: taking potassium dihydrogen phosphate water to dissolve and is diluted to 1000mL, with phosphorus acid for adjusting pH value
To 2.2-2.6.
2. phthalic anhydride according to claim 1 and its detection method in relation to substance, it is characterised in that: the gradient elution
Process are as follows: in 0~30min, volume ratio 84:16~87:13 of mobile phase A and Mobile phase B；In 30~50min, mobile phase A and
The volume ratio of Mobile phase B is from 85:15 at the uniform velocity gradual change to 20:80；In 50~51min, the volume ratio of mobile phase A and Mobile phase B
From 20:80 at the uniform velocity gradual change to 85:15；In 51~70min, the volume ratio of mobile phase A and Mobile phase B is 85:15.
3. phthalic anhydride according to claim 1 and its detection method in relation to substance, it is characterised in that: in mobile phase A, phosphoric acid
The concentration of dihydro potassium solution is 0.55g/L~0.67g/L.
4. the phthalic anhydride stated according to claim 3 and its detection method in relation to substance, it is characterised in that: the potassium dihydrogen phosphate is molten
The concentration of liquid is 0.61g/L.
5. the phthalic anhydride stated according to claim 1 and its detection method in relation to substance, it is characterised in that: in the 0~30min,
The volume ratio 85:15 of mobile phase A and Mobile phase B.
6. phthalic anhydride according to claim 1 and its detection method in relation to substance, it is characterised in that: the length of the chromatographic column
Degree is 250mm, and diameter 4.6mm, packing material size is 5 μm.
7. phthalic anhydride according to claim 1 and its detection method in relation to substance, it is characterised in that: the Detection wavelength is
230nm。
8. phthalic anhydride according to claim 1 and its detection method in relation to substance, it is characterised in that: the column temperature is 35
℃。
9. phthalic anhydride according to claim 1 and its detection method in relation to substance, it is characterised in that: the flow velocity is
1.0mL/min。
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Cited By (2)
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| CN111220730A (en) * | 2020-01-19 | 2020-06-02 | 合肥科颖医药科技有限公司 | Analysis method of related substances in irbesartan and hydrochlorothiazide compound preparation |
| CN113049699A (en) * | 2021-03-17 | 2021-06-29 | 北京鑫开元医药科技有限公司 | Method for detecting biphenyl anhydride and related substances thereof and application |
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| US20110150986A1 (en) * | 2009-12-18 | 2011-06-23 | Kristin Arnold | Quinine formulations, method of making, and metho of use thereof |
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| CN111220730A (en) * | 2020-01-19 | 2020-06-02 | 合肥科颖医药科技有限公司 | Analysis method of related substances in irbesartan and hydrochlorothiazide compound preparation |
| CN113049699A (en) * | 2021-03-17 | 2021-06-29 | 北京鑫开元医药科技有限公司 | Method for detecting biphenyl anhydride and related substances thereof and application |
| CN113049699B (en) * | 2021-03-17 | 2022-09-30 | 北京鑫开元医药科技有限公司 | Method for detecting biphenyl anhydride and related substances thereof and application |
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Application publication date: 20190409 |