CN102507758B - Detection method of cis-trans isomer in cis-propenyl phosphonic acid and related impurity thereof - Google Patents
Detection method of cis-trans isomer in cis-propenyl phosphonic acid and related impurity thereof Download PDFInfo
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Abstract
A detection method of cis-trans isomers in cis-propenyl phosphonic acid and related impurities thereof is applicable to the field of pharmaceutical analysis, and the method comprises the following steps and conditions: the chromatographic conditions are that the chromatographic column is a C-18 column of 4.6 mm*250 mm*5.0 microns; the flow velocity is 1.0 ml/min; an ultraviolet detector has a detection wavelength of 225 nm and a sample size of 10 microliters; the mobile phase is 50 mmol/L dipotassium hydrogen phosphate aqueous solution-methanol; preparing a test solution by dissolving 0.1 microliters of test samples in the mobile phase, diluting to 25 ml, and filtering; introducing 10 microliters of the test solution, recording a spectrum, wherein the retention time for cis-propenyl phosphonic acid is 12.3 min, the relative retention value of its cis-trans isomers is 1.15, and the relative retention value of propadiene phosphonic acid is 0.38, and calculating the contents of various impurities by an area normalization method; in the mobile phase, the 50 mmol/L dipotassium hydrogen phosphate aqueous solution contains 2% of tetrabutylammonium hydroxide aqueous solutions; the concentration of the tetrabutylammonium hydroxide aqueous solution is 55%. According to the invention, the method is used for the detection of cis-trans isomers in cis-propenyl phosphonic acid and related impurities thereof, and the repeatability, the sensitivity, and the accuracy all meet the requirements.
Description
Technical field
The invention belongs to the Pharmaceutical Analysis field, be specifically related to the detection method of cis-trans-isomer in a kind of cis-propene phosphoric acid and related impurities thereof.
Background technology
At present, phosphonomycin 1,2-phosphate epoxypropyl disodium salt are a kind of free acids, separate from Streptomyces fradicle at first, and be effective to Gram-positive and negative bacterium, and its mechanism of action is that suppress bacteria cell wall synthetic causes bacterium death.Phosphonomycin can combine with a kind of bacteria cell wall synzyme, hinder the first step reaction that bacterium utilizes related substance synthetic cell wall, thereby play bactericidal action, the phosphonomycin antimicrobial spectrum is wider, be mainly used in responsive microbial respiratory tract, the urinary tract, enteron aisle and skin soft-tissue infections such as golden grape bacterium, Escherichia coli, pneumonia thunder uncle bacterium, aerobacteria, Serratia, Shigella, pseudomonas aeruginosa, and septicemia, peritonitis, meningitis etc.Its curative effect is only second to penicillins in sum, and the chance that anaphylactic shock takes place is very few.So be subjected to vast medical worker and patient's welcome, use clinic and the individual of phosphonomycin to be seen everywhere.
Cis-propene phosphoric acid is the intermediate of preparation phosphonomycin, and propadiene phosphoric acid is the precursor of cis-propene phosphoric acid, and in the preparation process of phosphonomycin, the content of the trans isomer in the cis-propene phosphoric acid and propadiene phosphoric acid directly has influence on yield and the quality of phosphonomycin series of products.For guaranteeing quality and the security thereof of medicine, need set up detection method the content of the trans isomer in cis-propene phosphoric acid, the cis-propene phosphoric acid in the phosphonomycin and propadiene phosphoric acid is controlled.At present, the detection method of cis-trans-isomer and related impurities thereof is not seen relevant report in the cis-propene phosphoric acid.Therefore, the detection method of developing cis-trans-isomer in a kind of cis-propene phosphoric acid and related impurities thereof is the new problem that needs to be resolved hurrily always.
Summary of the invention
The object of the present invention is to provide the detection method of cis-trans-isomer in a kind of cis-propene phosphoric acid and related impurities thereof, this method adopts the content of cis-trans-isomer in the high performance liquid chromatography monitoring cis-propene phosphoric acid and precursor propadiene phosphoric acid thereof, to guarantee to produce sustainedly and stably the specification product of quality homogeneous.
The object of the present invention is achieved like this: the detection method of cis-trans-isomer and related impurities thereof in a kind of cis-propene phosphoric acid, described method comprises the steps:
(1) chromatographic condition:
Chromatographic column: C-18 post, 4.6mm * 250mm * 5.0 μ m; Flow velocity 1.0ml/min; UV-detector detects wavelength 225nm, sample size 10 μ l;
Aqueous dibasic potassium phosphate solution-methyl alcohol of mobile phase: 50mmol/L;
(2) test liquid preparation: get test sample 0.1 μ l, with mobile phased soln and be diluted to 25ml, filtration;
(3) get test liquid, sample introduction 10 microlitres, the record collection of illustrative plates, the cis-propene phosphoric acid retention time is 12.3min, and its cis-trans-isomer relative retention value is 1.15, and propadiene phosphoric acid relative retention value is 0.38, adopts area normalization method to calculate each impurity content;
Contain 2% TBAH aqueous solution in the aqueous dibasic potassium phosphate solution of described mobile middle 50mmol/L mutually; The concentration of described TBAH aqueous solution is 55%; The pH of described mobile phase aqueous dibasic potassium phosphate solution needs to be transferred to 7.0 with phosphoric acid; Described mobile phase aqueous dibasic potassium phosphate solution and methyl alcohol volume ratio are 90:10; Described detection method is identified cis-propene phosphoric acid and cis-trans-isomer thereof, propadiene phosphoric acid according to retention time and relative retention value.
Main points of the present invention are its detection method.The ultimate principle of this detection method is that cis-propene phosphoric acid, propadiene phosphoric acid, the retention time difference of cis-propene phosphoric acid trans-isomer in flowing mutually utilize the HPLC detection method to calculate its content respectively.
The detection method of cis-trans-isomer and related impurities thereof compared with prior art in a kind of cis-propene phosphoric acid, have by this method and detect cis-trans-isomer and related impurities thereof in the cis-propene phosphoric acid, advantages such as reappearance, sensitivity, accuracy all can meet the requirements will be widely used in the Pharmaceutical Analysis field.
Embodiment
Following example will help understanding of the present invention, but these examples are only in order to be illustrated the present invention, and the present invention is not limited to these contents.
The detection method of cis-trans-isomer and related impurities thereof in a kind of cis-propene phosphoric acid, described method comprises the steps:
(1) chromatographic condition:
Chromatographic column: C-18 post, 4.6mm * 250mm * 5.0 μ m; Flow velocity 1.0ml/min; UV-detector detects wavelength 225nm, sample size 10 μ l;
Aqueous dibasic potassium phosphate solution-methyl alcohol of mobile phase: 50mmol/L;
(2) test liquid preparation: get test sample 0.1 μ l, with mobile phased soln and be diluted to 25ml, filtration;
(3) get test liquid, sample introduction 10 microlitres, the record collection of illustrative plates, the cis-propene phosphoric acid retention time is 12.3min, and its cis-trans-isomer relative retention value is 1.15, and propadiene phosphoric acid relative retention value is 0.38, adopts area normalization method to calculate each impurity content;
Contain 2% TBAH aqueous solution in the aqueous dibasic potassium phosphate solution of described mobile middle 50mmol/L mutually; The concentration of described TBAH aqueous solution is 55%; The pH of described mobile phase aqueous dibasic potassium phosphate solution needs to be transferred to 7.0 with phosphoric acid; Described mobile phase aqueous dibasic potassium phosphate solution and methyl alcohol volume ratio are 90:10; Described detection method is identified cis-propene phosphoric acid and cis-trans-isomer thereof, propadiene phosphoric acid according to retention time and relative retention value.
Be further described in detail below in conjunction with the present invention of embodiment:
1. the preparation of related solution and the phase that flows:
1.1 the preparation of the phase that flows: get potassium dihydrogen phosphate 6.8g, add water and dissolve in right amount, adding 20.0ml mass percent concentration is 55% TBAH aqueous solution, is diluted with water to 1000ml, regulates pH to 7.0 with phosphoric acid.Measure this liquid 900ml, mix with 100ml methyl alcohol, filter, the degassing.
1.2 need testing solution preparation
1.2.1 get test sample (lot number: 1) 0.1ml, with mobile phased soln and be diluted to 25ml, filter.
1.2.2 get test sample (lot number: 2) 0.1ml, with mobile phased soln and be diluted to 25ml, filter.
1.2.3 get test sample (lot number: 3) 0.1ml, with mobile phased soln and be diluted to 25ml, filter.
2. assay method
Each 10 μ l injects liquid chromatograph respectively with 3 batches of need testing solutions, the record collection of illustrative plates.The cis-propene phosphoric acid retention time is 12.3min, and its cis-trans-isomer relative retention value is 1.15, and propadiene phosphoric acid relative retention value is 0.38.Adopt area normalization method to calculate each impurity content.
3. testing result:
Test sample 1
The peak area of propadiene phosphoric acid is 811140, and the peak area of cis-propene phosphoric acid is 3436614,
The peak area of cis-propene phosphoric acid trans-isomer is 1409248
Propadiene phosphorus acid content=811140 ÷ (811140+3436614+1409248) * 100%=14.34%
Cis-propene phosphoric acid content=3436614 ÷ (811140+3436614+1409248) * 100%=60.75%
Cis-propene phosphoric acid trans-isomer content=1409248 ÷ (811140+3436614+1409248) * 100%=24.91%
Test sample 2
The peak area of propadiene phosphoric acid is 831520, and the peak area of cis-propene phosphoric acid is 3386510,
The peak area of cis-propene phosphoric acid trans-isomer is 1438236
Propadiene phosphorus acid content=831520 ÷ (831520+3386510+1438236) * 100%=14.70%
Cis-propene phosphoric acid content=3386510 ÷ (831520+3386510+1438236) * 100%=59.87%
Cis-propene phosphoric acid trans-isomer content=1438236 ÷ (831520+3386510+1438236) * 100%=25.43%
Test sample 3
The peak area of propadiene phosphoric acid is 820377, and the peak area of cis-propene phosphoric acid is 3356745,
The peak area of cis-propene phosphoric acid trans-isomer is 1436502
Propadiene phosphorus acid content 1=820377 ÷ (820377+3356745+1436502) * 100%=14.61%
Cis-propene phosphoric acid content 1=3356745 ÷ (820377+3356745+1436502) * 100%=59.80%
Cis-propene phosphoric acid trans-isomer content=1436502 ÷ (820377+3356745+1436502) * 100%=25.59%
Claims (2)
1. the detection method of cis-trans-isomer and related impurities thereof in the cis-propene phosphoric acid, it is characterized in that: described method comprises the steps:
(1) chromatographic condition:
Chromatographic column: C-18 post, 4.6mm * 250mm * 5.0 μ m; Flow velocity 1.0ml/min; UV-detector detects wavelength 225nm, sample size 10 μ l;
Aqueous dibasic potassium phosphate solution-methyl alcohol of mobile phase: 50mmol/L; Contain 2% TBAH aqueous solution in the aqueous dibasic potassium phosphate solution of described mobile middle 50mmol/L mutually; The concentration of described TBAH aqueous solution is 55%; The pH of described mobile phase aqueous dibasic potassium phosphate solution needs to be transferred to 7.0 with phosphoric acid; Described mobile phase aqueous dibasic potassium phosphate solution and methyl alcohol volume ratio are 90:10;
(2) test liquid preparation: get test sample 0.1 μ l, with mobile phased soln and be diluted to 25ml, filtration;
(3) get test liquid, sample introduction 10 microlitres, the record collection of illustrative plates, the cis-propene phosphoric acid retention time is 12.3min, and its cis-trans-isomer relative retention value is 1.15, and propadiene phosphoric acid relative retention value is 0.38, adopts area normalization method to calculate each impurity content.
2. according to the detection method of cis-trans-isomer and related impurities thereof in the described a kind of cis-propene phosphoric acid of claim 1, it is characterized in that: described detection method is identified cis-propene phosphoric acid and cis-trans-isomer thereof, propadiene phosphoric acid according to retention time and relative retention value.
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| CN106872589B (en) * | 2017-01-03 | 2019-04-02 | 江苏开元医药化工有限公司 | A kind of detection method of the right phenyl ethylamine salt of left phosphonomycin and its enantiomter |
| CN110672772B (en) * | 2019-11-01 | 2022-03-15 | 上海峰林生物科技有限公司 | Detection and judgment method for cis-propenyl phosphonic acid ethanol solution |
| CN110887925B (en) * | 2019-12-03 | 2022-03-15 | 上海峰林生物科技有限公司 | High performance liquid chromatography method for determining fosfomycin sodium impurities |
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