CN103245744A - Method for detecting related substances in azithromycin for injection - Google Patents
Method for detecting related substances in azithromycin for injection Download PDFInfo
- Publication number
- CN103245744A CN103245744A CN2013101728191A CN201310172819A CN103245744A CN 103245744 A CN103245744 A CN 103245744A CN 2013101728191 A CN2013101728191 A CN 2013101728191A CN 201310172819 A CN201310172819 A CN 201310172819A CN 103245744 A CN103245744 A CN 103245744A
- Authority
- CN
- China
- Prior art keywords
- azithromycin
- test
- injection
- solution
- injection rate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Landscapes
- Saccharide Compounds (AREA)
Abstract
The invention relates to the field of a drug, and in particular relates to a method for detecting related substances in azithromycin for injection. The method comprises the steps of: diluting an azithromycin B reference substance into a solution by sodium chloride injection, orderly carrying out an abnormal toxicity control method test on the solution according to the ascending order of the injection amount, and setting the injection amount in a previous test of the test to be injection amount extreme of the azithromycin B until a mice death result appears in a retest of the test of the azithromycin B injection amount; measuring the injection extremes of azithromycin Gx and erythrocin A iminoether according to the same method; carrying out quantitative analysis on the content C of three substances and the azithromycin in the drug to be tested; calculating according to each maximal dosage and formula to obtain the impurity extremes W1, W2 and W3 of three related substances; if the content of one related substance is not more than W1, not more than W2 and not more than W3, judging that the content of the related substance of the drug achieves the safety level, or else, judging that the content does not achieve the safety level. The target of quantitative evaluation is achieved by the method.
Description
Technical field
The present invention relates to drug world, the inspection method of related substance in the azithromycin injection.
Background technology
The inspection of related substance is an important indicator estimating its security in the azithromycin injection.Related substance mainly refers to azithromycin B, azithromycin G in the azithromycin injection
x, Erythromycin A iminoether etc.
In the correlation technique, the inspection of related substance is to adopt thin-layered chromatography (TLC) in the azithromycin injection: with test sample (azithromycin injection) and contrast liquid point sample on silica gel g thin-layer plate respectively, judge by comparison both amount of speckle and shade whether its related substances reaches security level.Kind and concentration that various inspection methods just will contrast liquid change slightly, and used principle is all identical, for example, and national drug standards WS
1-(X-296)-2003Z:
Get test sample (azithromycin injection), make the solution that every 1ml contains azithromycin 20mg with anhydrous alcohol solution and dilution, as need testing solution; Get need testing solution and erythromycin standard items, make the solution that contains azithromycin and each 0.4mg of erythromycin among every 1ml, solution (1) in contrast with anhydrous alcohol solution and dilution; Other gets two parts of need testing solutions, makes the solution that every 1ml contains azithromycin 0.6mg and 0.2mg with absolute ethyl alcohol respectively, in contrast solution (2) and (3).Accurate each the 10 μ l of above-mentioned four kinds of solution that draw, put respectively on same silica gel g thin-layer plate, be developping agent with ethyl acetate-normal hexane-diethylamine (10:10:2), dry after the expansion, spray (is got sodium molybdate 2.5g, cerous sulfate 1g with developer, add the dissolving of 10% sulfuric acid solution and be diluted to 100ml), put 105 ℃ of heating several minutes.Azithromycin separates fully with the erythromycin spot in contrast solution (1), the impurity spot of need testing solution is no more than 3, and the color of each impurity spot and the principal spot of contrast solution are relatively, a maximum impurity spot is not deeper than the principal spot (3%) of contrast solution (2), when other two impurity spots are not deeper than the principal spot (1%) of contrast solution (3) respectively, this test sample its related substances reaches security level, otherwise does not reach security level.
By above as can be known, the inspection method in the correlation technique can only realize the purpose of semi-quantitative assessment its related substances, can't realize quantitative evaluation, thereby can not more scientifically study, and for example influences the analysis of causes of its injection security etc.
Summary of the invention
The object of the present invention is to provide the inspection method of related substance in the azithromycin injection, to solve the above problems.
The inspection method of related substance in the azithromycin injection is provided in an embodiment of the present invention, has comprised the following steps:
Steps A: get azithromycin B reference substance, and with sodium chloride injection with the solution of its dilution for same concentration or variable concentrations, the order that increases progressively according to azithromycin B injection rate IR with these solution is carried out the test of undue toxicity inspection technique successively again, dead mouse occurs as a result the time in the retrial of the test of a certain azithromycin B injection rate IR, used azithromycin B injection rate IR is decided to be the injection rate IR limit of azithromycin B in the previous test with this test;
Step B: get azithromycin G
xReference substance, and with sodium chloride injection with the solution of its dilution for same concentration or variable concentrations, use these solution according to azithromycin G again
xThe order that injection rate IR increases progressively is carried out the test of undue toxicity inspection technique successively, until a certain azithromycin G
xDead mouse appears as a result the time, used azithromycin G in the previous test with this test in the retrial of the test of injection rate IR
xInjection rate IR is decided to be azithromycin G
xThe injection rate IR limit;
Step C: get Erythromycin A iminoether reference substance, and with sodium chloride injection with the solution of its dilution for same concentration or variable concentrations, the order that increases progressively according to Erythromycin A iminoether injection rate IR with these solution is carried out the test of undue toxicity inspection technique successively again, dead mouse occurs as a result the time in the retrial of the test of a certain Erythromycin A iminoether injection rate IR, used Erythromycin A iminoether injection rate IR is decided to be the injection rate IR limit of Erythromycin A iminoether in the previous test with this test;
Step D: the content C of azithromycin B in the quantitative test azithromycin injection to be measured
1, azithromycin G
xContent C
2, the Erythromycin A iminoether content C
3, azithromycin content C;
Step e: according to the each maximum consumption m of azithromycin injection to be measured, and following formula calculates, and obtains the l.o.i W of azithromycin B
1, azithromycin G
xL.o.i W
2L.o.i W with the Erythromycin A iminoether
3:
Step F: will
Respectively correspondingly with described W
1, W
2, W
3Compare; If
And
And
Then its related substances reaches security level in the described azithromycin injection to be measured, otherwise does not reach security level.
The inspection method of related substance in the azithromycin injection of the above embodiment of the present invention can realize azithromycin B in the quantitative check azithromycin injection, azithromycin G
x, three kinds of related substances of Erythromycin A iminoether purpose, be specially:
Described steps A has been measured azithromycin B, azithromycin G respectively to C employing undue toxicity inspection technique
x, three kinds of related substances of Erythromycin A iminoether the injection rate IR limit, and then obtain the l.o.i W of three kinds of related substances by described step e
1, W
2, W
3
Obtain the content C of three kinds of related substances again by the quantitative test of described step D
1, C
2, C
3, and the content C of the effective constituent azithromycin of this medicine;
Calculate in the azithromycin injection to be measured the content ratio of three kinds of related substances and effective constituent azithromycin at last, namely
Again with these three values respectively correspondingly with described W
1, W
2, W
3Compare, namely
With W
1,
With W
2,
With W
3Compare, if
And
And
Then its related substances reaches security level in the described azithromycin injection to be measured, otherwise does not reach security level;
Hence one can see that, and method of the present invention is by quantitative measurement azithromycin B, azithromycin G
x, three kinds of impurity related substances of Erythromycin A iminoether l.o.i, and the content of three kinds of related substances in the azithromycin injection to be measured has been realized the purpose of quantitative evaluation, this result can be used for other further research.
Description of drawings
Fig. 1 is the high-efficient liquid phase chromatogram of first sample described in the test example of the present invention;
Fig. 2 is the high-efficient liquid phase chromatogram of second sample described in the test example of the present invention.
Embodiment
Also by reference to the accompanying drawings the present invention is described in further detail below by specific embodiment.
Embodiment
Embodiments of the invention provide the inspection method of related substance in the azithromycin injection, comprise the following steps:
Step 101: get azithromycin B reference substance, and with sodium chloride injection with the solution of its dilution for same concentration or variable concentrations, the order that increases progressively according to azithromycin B injection rate IR with these solution is carried out the test of undue toxicity inspection technique successively again, dead mouse occurs as a result the time in the retrial of the test of a certain azithromycin B injection rate IR, used azithromycin B injection rate IR is decided to be the injection rate IR limit of azithromycin B in the previous test with this test;
Step 102: get azithromycin G
xReference substance, and with sodium chloride injection with the solution of its dilution for same concentration or variable concentrations, use these solution according to azithromycin G again
xThe order that injection rate IR increases progressively is carried out the test of undue toxicity inspection technique successively, until a certain azithromycin G
xDead mouse appears as a result the time, used azithromycin G in the previous test with this test in the retrial of the test of injection rate IR
xInjection rate IR is decided to be azithromycin G
xThe injection rate IR limit;
Step 103: get Erythromycin A iminoether reference substance, and with sodium chloride injection with the solution of its dilution for same concentration or variable concentrations, the order that increases progressively according to Erythromycin A iminoether injection rate IR with these solution is carried out the test of undue toxicity inspection technique successively again, dead mouse occurs as a result the time in the retrial of the test of a certain Erythromycin A iminoether injection rate IR, used Erythromycin A iminoether injection rate IR is decided to be the injection rate IR limit of Erythromycin A iminoether in the previous test with this test;
Step 104: the content C of azithromycin B in the quantitative test azithromycin injection to be measured
1, azithromycin G
xContent C
2, the Erythromycin A iminoether content C
3, azithromycin content C;
Step 105: according to the each maximum consumption m of azithromycin injection to be measured, and following formula calculates, and obtains the l.o.i W of azithromycin B
1, azithromycin G
xL.o.i W
2L.o.i W with the Erythromycin A iminoether
3:
Step 106: will
Respectively correspondingly with described W
1, W
2, W
3Compare; If
And
And
Then its related substances reaches security level in the described azithromycin injection to be measured, otherwise does not reach security level.
The inspection method of related substance in the azithromycin injection of above-described embodiment can realize azithromycin B in the quantitative check azithromycin injection, azithromycin G
x, three kinds of related substances of Erythromycin A iminoether purpose, be specially:
Described step 101 has been measured azithromycin B, azithromycin G respectively to 103 employing undue toxicity inspection techniques
x, three kinds of related substances of Erythromycin A iminoether the injection rate IR limit, and then obtain the l.o.i W of three kinds of related substances by described step 105
1, W
2, W
3
Obtain the content C of three kinds of related substances again by the quantitative test of described step 104
1, C
2, C
3, and the content C of the effective constituent azithromycin of this medicine;
Calculate in the azithromycin injection to be measured the content ratio of three kinds of related substances and effective constituent azithromycin at last, namely
Again with these three values respectively correspondingly with described W
1, W
2, W
3Compare, namely
With W
1,
With W
2,
With W
3Compare, if
And
And
Then its related substances reaches security level in the described azithromycin injection to be measured, otherwise does not reach security level;
Hence one can see that, and method of the present invention is by quantitative measurement azithromycin B, azithromycin G
x, three kinds of related substances of Erythromycin A iminoether l.o.i, and the content of three kinds of related substances in the azithromycin injection to be measured has been realized the purpose of quantitative evaluation, this result can be used for other further research.As seen, the present invention provides a new science approach for the safety evaluatio of related substance in the medicine, and this method can also be for other related substance that checks azithromycin injection, and concrete test condition can draw by the test of limited number of time.
Wherein, described undue toxicity inspection technique is referring to Pharmacopoeia of the People's Republic of China version appendix in 2010 XIC: 5 of healthy mices getting body weight and be 17-20g, reference substance solution is injected mouse tail vein, should 4-5 in second at the uniform velocity injection finish dead mouse situation in 48 hours after the record administration; During if any death, other gets 10 retrials of healthy mice of body weight 18-19g, dead mouse situation in 48 hours after the record administration.
Described m can be different at different treatment targets, and common people are 0.5g with the m of this medicine.(can referring to the instructions of specific product)
Described quantitative analysis method can be adopted high efficiency liquid phase chromatographic analysis method, and perhaps other is suitable for the method for three kinds of related substances of quantitative measurment and effective constituent.
The described step 101 of said method is in 103, and reference substance dilution per step is corresponding with sodium chloride injection is the solution of variable concentrations, gets the order that these solution of same dose increase progressively according to concentration again and carries out the test of undue toxicity inspection technique successively.Adopt the mode of this " dosage is identical, concentration is different " to change injection rate IR, can reduce the influence of the other factors between each test group, the accuracy of raising method.
When described step 104 used high efficiency liquid phase chromatographic analysis method to carry out quantitative test, for further accuracy, the science of this inspection method, this method can also be improved in the following areas.
(1) preferably, described high performance liquid chromatography detects C
1, C
2, C
3, the used filling agent of C is octadecylsilane chemically bonded silica, used flowing is the mixture of acetonitrile-phosphate buffer that volume ratio is 45:55 mutually; The detection wavelength is 210nm.Through evidence, adopt this analysis condition, analysis result accuracy and degree of accuracy are higher, and detection time is short.
(2) preferably, the pH value of described phosphate buffer is 8.2-8.4, wherein more preferably is 8.2.Through evidence, adopt the damping fluid of this pH value, detection time is shorter, has improved detection efficiency.Wherein, preferably, the compound method of described phosphate buffer is: get the 0.05mol/L dipotassium hydrogen phosphate solution, regulate pH value to 8.2 with the phosphoric acid solution of 0.2g/mL, the used two kinds of reagent costs of this method are low, and easily acquisition, reduced experimentation cost.
(3) preferably, described high performance liquid chromatography is: with acetonitrile azithromycin injection to be measured being diluted is certain density solution, as first sample; Again first test sample is diluted n doubly as second sample; Inject described first sample to high performance liquid chromatograph, detect C
1, C
2, C
3In high performance liquid chromatograph, inject described second sample, detect C; Described n is 50-150.Azithromycin and the solubleness height of three kinds of related substances in acetonitrile are more conducive to detect.And the solution that adopts variable concentrations simultaneously detects three kinds of materials and effective constituent respectively, can improve the accuracy of method: related substance (impurity) content in the common azithromycin injection to be measured is lower, be that the concentration of three kinds of related substances in the same solution and the concentration of azithromycin have big difference, if adopt the solution of same concentration to detect this four kinds of materials simultaneously, can exceed the detectability of instrument or too near the detectability of instrument, the accuracy of reduction method.
(4) preferably, the concentration of azithromycin injection is 8-10mg/mL in described first sample, and described n=100.Through evidence, accuracy and the precision of this detection method are higher.In like manner, preferably, the injection rate IR of described first sample and second sample is 50 μ L.
In order to illustrate in greater detail the performance of method of the present invention, below also provide concrete test example.
The test example
Test method:
Undue toxicity inspection technique test: get azithromycin B, azithromycin G respectively
x, Erythromycin A iminoether reference substance, make the solution of variable concentrations with sodium chloride injection, get 5 of healthy mices (body weight 17-20g), need testing solution is injected mouse tail vein, should at the uniform velocity inject second at 4-5 and finish, every mouse gives need testing solution 0.5ml respectively, dead mouse situation in 48 hours after the record administration; During if any death, other gets 10 retrials of healthy mice of body weight 18-19g, dead mouse situation in 48 hours after the record administration.
The high performance liquid chromatography test:
Precision takes by weighing azithromycin injection 98.21mg, adds acetonitrile dissolving and dilution and makes the solution that concentration is 9.821mg/ml, as first sample; Precision is measured 1ml, puts in the 100ml volumetric flask,, shake up to scale with dilution in acetonitrile, and as second sample, be filling agent with octadecylsilane chemically bonded silica; (volume ratio is 45:55) for flowing phase with phosphate buffer (get the 0.05mol/L dipotassium hydrogen phosphate solution, the phosphoric acid solution with 20% is regulated pH value to 8.2)-acetonitrile; The detection wavelength is 210nm, and precision is measured each 50 μ L of first sample and second sample, injects liquid chromatograph respectively, 2 times of record chromatogram (peak of azithromycin) retention time to the major component peak.
Because azithromycin B, azithromycin G
x, the absorptivity of four kinds of materials of Erythromycin A iminoether and azithromycin under same liquid phase testing conditions be different, so for the ease of the comparison of later stage four kinds of material concentrations, this test has also detected azithromycin B, azithromycin G
x, three kinds of materials of Erythromycin A iminoether are with respect to the correction factor f of azithromycin.
The measuring method of f: get azithromycin and impurity azithromycin B, azithromycin G
x, four materials of Erythromycin A iminoether reference substance each is an amount of, put and add mobile phase in the same volumetric flask { phosphate buffer (is got the 0.05mol/L dipotassium hydrogen phosphate solution, phosphoric acid solution with 20% is regulated pH value to 8.2)-acetonitrile (45:55) } dissolving, and be diluted to the solution that four kinds of materials respectively contain about 10mg/ml, as mixed solution.Measure above-mentioned mixed solution 50 μ l and inject liquid chromatograph, the record chromatogram, read the correction factor that each material peak-to-peak area is calculated as follows each impurity:
M
Impurity: the title sample quality of impurity
M
Archie: the title sample quality of azithromycin
A
Impurity: the peak area of impurity
A
Archie: the peak area of azithromycin
Test findings:
Undue toxicity inspection technique test: by table one to table three as can be known, azithromycin B injection rate IR limit is 3.73mg, azithromycin G
xThe injection rate IR limit is 1.91mg, and Erythromycin A iminoether injection rate IR limit is 1.75mg.
This test is with artificial medicine use object in the future, and the each maximum consumption m of its azithromycin injection is 0.5g.The l.o.i that obtains azithromycin B thus is 0.746%(3.73/500), azithromycin G
xL.o.i be 0.382%(1.91/500), the l.o.i of Erythromycin A iminoether is 0.35%(1.75/500).
The undue toxicity experiment of table one azithromycin B reference substance
Table two azithromycin G
xThe undue toxicity experiment of reference substance
The undue toxicity experiment of table three Erythromycin A iminoether reference substance
The high performance liquid chromatography test:
As depicted in figs. 1 and 2, azithromycin B, azithromycin G
x, the retention time of Erythromycin A iminoether, azithromycin is respectively: 24.856,9.786,4.216,15.630.Fig. 1 is the chromatogram of described first sample; Fig. 2 is the chromatogram of described second sample.
The correction factor of each impurity as shown in Table 4.
Each impurity correction factor measurement result of table four
| The impurity title | Azithromycin B | Azithromycin G x | The Erythromycin A iminoether |
| Correction factor | 1.01 | 0.11 | 0.42 |
At last, with azithromycin B, azithromycin G in described first sample
x, the Erythromycin A iminoether peak area multiply by separately correction factor respectively, because the concentration of described first sample is 100 times of described second sample, peak area with azithromycin in described second sample multiply by 100 again, peak area with above-mentioned corrected three impurity is divided by again, obtain the content ratio of three kinds of impurity and azithromycin: azithromycin B is 0.434%, azithromycin G
xBe 0.148%, the Erythromycin A iminoether is 0.179%, the l.o.i of these three values and abnormal toxicity test gained is compared correspondingly: 0.434%＜0.746%, 0.148%＜0.382%, 0.179%＜0.35%.
The content of the azithromycin injection product related substance that as seen, checks in this test example reaches security level.
The above is the preferred embodiments of the present invention only, is not limited to the present invention, and for a person skilled in the art, the present invention can have various changes and variation.Within the spirit and principles in the present invention all, any modification of doing, be equal to replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (10)
1. the inspection method of related substance in the azithromycin injection is characterized in that, comprises the following steps:
Steps A: get azithromycin B reference substance, and with sodium chloride injection with the solution of its dilution for same concentration or variable concentrations, the order that increases progressively according to azithromycin B injection rate IR with these solution is carried out the test of undue toxicity inspection technique successively again, dead mouse occurs as a result the time in the retrial of the test of a certain azithromycin B injection rate IR, used azithromycin B injection rate IR is decided to be the injection rate IR limit of azithromycin B in the previous test with this test;
Step B: get azithromycin G
xReference substance, and with sodium chloride injection with the solution of its dilution for same concentration or variable concentrations, use these solution according to azithromycin G again
xThe order that injection rate IR increases progressively is carried out the test of undue toxicity inspection technique successively, until a certain azithromycin G
xDead mouse appears as a result the time, used azithromycin G in the previous test with this test in the retrial of the test of injection rate IR
xInjection rate IR is decided to be azithromycin G
xThe injection rate IR limit;
Step C: get Erythromycin A iminoether reference substance, and with sodium chloride injection with the solution of its dilution for same concentration or variable concentrations, the order that increases progressively according to Erythromycin A iminoether injection rate IR with these solution is carried out the test of undue toxicity inspection technique successively again, dead mouse occurs as a result the time in the retrial of the test of a certain Erythromycin A iminoether injection rate IR, used Erythromycin A iminoether injection rate IR is decided to be the injection rate IR limit of Erythromycin A iminoether in the previous test with this test;
Step D: the content C of azithromycin B in the quantitative test azithromycin injection to be measured
1, azithromycin G
xContent C
2, the Erythromycin A iminoether content C
3, azithromycin content C;
Step e: according to the each maximum consumption m of azithromycin injection to be measured, and following formula calculates, and obtains the l.o.i W of azithromycin B
1, azithromycin G
xL.o.i W
2L.o.i W with the Erythromycin A iminoether
3:
Step F: will
Respectively correspondingly with described W
1, W
2, W
3Compare; If
And
And
Then its related substances reaches security level in the described azithromycin injection to be measured, otherwise does not reach security level.
2. method according to claim 1, it is characterized in that, described steps A is to C, and reference substance dilution per step is corresponding with sodium chloride injection is the solution of variable concentrations, gets the order that these solution of same dose increase progressively according to concentration again and carries out the test of undue toxicity inspection technique successively.
3. according to each described method of claim 1-2, it is characterized in that the method for the quantitative test among the described step D is:
High efficiency liquid phase chromatographic analysis method.
4. method according to claim 3 is characterized in that, described high performance liquid chromatography detects C
1, C
2, C
3, the used filling agent of C is octadecylsilane chemically bonded silica, used flowing is the mixture of acetonitrile-phosphate buffer that volume ratio is 45:55 mutually; The detection wavelength is 210nm.
5. method according to claim 4 is characterized in that, the pH value of described phosphate buffer is 8.0-8.4.
6. method according to claim 5 is characterized in that, the pH value of described phosphate buffer is 8.2.
7. method according to claim 6 is characterized in that, the compound method of described phosphate buffer is: get the 0.05mol/L dipotassium hydrogen phosphate solution, regulate pH value to 8.2 with the phosphoric acid solution of 0.2g/mL.
8. method according to claim 7 is characterized in that, described high performance liquid chromatography is:
With acetonitrile azithromycin injection to be measured being diluted is certain density solution, as first sample; Again first test sample is diluted n doubly as second sample; Inject described first sample to high performance liquid chromatograph, detect C
1, C
2, C
3In high performance liquid chromatograph, inject described second sample, detect C;
Described n is 50-150.
9. method according to claim 8 is characterized in that, the concentration of azithromycin injection is 8-10mg/mL in described first sample, and described n=100.
10. method according to claim 9 is characterized in that, the injection rate IR of described first sample and second sample is 50 μ L.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310172819.1A CN103245744B (en) | 2013-05-10 | 2013-05-10 | Method for detecting related substances in azithromycin for injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310172819.1A CN103245744B (en) | 2013-05-10 | 2013-05-10 | Method for detecting related substances in azithromycin for injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103245744A true CN103245744A (en) | 2013-08-14 |
| CN103245744B CN103245744B (en) | 2015-01-07 |
Family
ID=48925396
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310172819.1A Active CN103245744B (en) | 2013-05-10 | 2013-05-10 | Method for detecting related substances in azithromycin for injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103245744B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104730153A (en) * | 2013-12-20 | 2015-06-24 | 辰欣药业股份有限公司 | Method for determining content of azithromycin for injection and related substances by high performance liquid chromatography |
| CN109633034A (en) * | 2019-01-29 | 2019-04-16 | 宜昌东阳光药业股份有限公司 | The detection method of azithromycin genotoxicity impurity |
| CN109870528A (en) * | 2019-02-21 | 2019-06-11 | 北京悦康科创医药科技股份有限公司 | A kind of method of the azithromycin capsules by HPLC in relation to substance |
| CN111024844A (en) * | 2019-12-18 | 2020-04-17 | 湖北省宏源药业科技股份有限公司 | Method for detecting related impurities of azithromycin capsules |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1878432A1 (en) * | 2003-07-24 | 2008-01-16 | Pliva - Research and Development Ltd. | Single dose fast dissolving azithromycin |
-
2013
- 2013-05-10 CN CN201310172819.1A patent/CN103245744B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1878432A1 (en) * | 2003-07-24 | 2008-01-16 | Pliva - Research and Development Ltd. | Single dose fast dissolving azithromycin |
Non-Patent Citations (4)
| Title |
|---|
| FUAD AL-RIMAWI ET AL.: "Analysis of Azithromycin and Its Related Compounds by RP-HPLC with UV Detection", 《JOURNAL OF CHROMATOGRAPHIC SCIENCE》 * |
| 何伍等: "浅谈药物杂质限度的制订方法", 《中国医药工业杂志》 * |
| 国家药典编委会: "《中华人民共和国药典》", 31 January 2010 * |
| 寇晋萍等: "阿奇霉素有关物质测定方法的优化", 《中国抗生素》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104730153A (en) * | 2013-12-20 | 2015-06-24 | 辰欣药业股份有限公司 | Method for determining content of azithromycin for injection and related substances by high performance liquid chromatography |
| CN109633034A (en) * | 2019-01-29 | 2019-04-16 | 宜昌东阳光药业股份有限公司 | The detection method of azithromycin genotoxicity impurity |
| CN109633034B (en) * | 2019-01-29 | 2021-05-14 | 宜昌东阳光生化制药有限公司 | Method for detecting azithromycin genotoxic impurity |
| CN109870528A (en) * | 2019-02-21 | 2019-06-11 | 北京悦康科创医药科技股份有限公司 | A kind of method of the azithromycin capsules by HPLC in relation to substance |
| CN111024844A (en) * | 2019-12-18 | 2020-04-17 | 湖北省宏源药业科技股份有限公司 | Method for detecting related impurities of azithromycin capsules |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103245744B (en) | 2015-01-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103245744B (en) | Method for detecting related substances in azithromycin for injection | |
| Pandya et al. | Development and validation of RP-HPLC method for determination of rosuvastatin calcium in bulk and pharmaceutical dosage form | |
| CN105424822B (en) | The method for detecting (1R, 2S) 2 (3,4 difluorophenyl) cyclopropylamine in ticagrelor | |
| CN104122363A (en) | Measuring method of mecobalamin tablet related substance | |
| CN102798678B (en) | Detection method and content determining method of sodium calcium edetate in pantoprazole sodium for injecting | |
| CN104090045A (en) | Method for simultaneously and quantitatively detecting ligustilide and senkyunolide A | |
| CN107884498A (en) | Liquid phase chromatography analytical method that is a kind of while determining procaine, penicillin and content of streptomycin | |
| CN106950306A (en) | A kind of method of cysteine content in measure Amino Acid Compound Injection | |
| CN105388225A (en) | Analysis and detection method for UDPC in medicinal preparation containing citicoline sodium | |
| CN100580448C (en) | Method for determining human plasma phenytoin and its precursor drug and metabolite | |
| El-Gindy et al. | Optimization and validation of a stability-indicating RP-HPLC method for determination of azithromycin and its related compounds | |
| CN103245745A (en) | Method for checking erythromycin A and imino ether in azithromycin for injection | |
| CN106290598B (en) | The high efficient liquid phase analysis method of impurity in a kind of Gadoversetamide | |
| CN103163228A (en) | Efficient liquid phase analysis method for hydroxyfasudil and preparation thereof | |
| Rane et al. | Stability-indicating RP-HPLC method for analysis of eplerenone in the bulk drug and in a pharmaceutical dosage form | |
| CN102788863B (en) | Detection method of compound preparation containing compound Zingiber corallinum Hance solution and urea miconazole ointment | |
| Ramathilagam et al. | Development and validation of HPLC method for the estimation of tolterodine tartrate in tablets | |
| CN104101663A (en) | Method for testing ebastine-related substances by high performance liquid chromatography | |
| CN104897833B (en) | A kind of detection method of ACT-064992 intermediate and its application | |
| Kulikov et al. | Development and validation of a micellar liquid chromatographic method with UV detection for determination of azithromycin in tablets and capsules | |
| CN102928525A (en) | Method for detecting related substance II of cefpirome in cefpirome sulfate/sodium chloride injection | |
| Hasin et al. | Validation of high performance liquid chromatography (HPLC) method for determination of erlotinib related substance in pharmaceutical dosage form | |
| Miron et al. | HPLC with diode-array detection for determination of leflunomide in tablets | |
| Madhusudhan et al. | Method development and validation of Alfuzosin HCl and Dutasteride in pharmaceutical dosage form by RP-HPLC | |
| Ravisankar et al. | A validated RPHPLC method for the assay of Prulifloxacin in marketed drug product using Levofloxacin as an internal standard |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Test method for related substances in azithromycin for injection Effective date of registration: 20230105 Granted publication date: 20150107 Pledgee: Bank of China Co.,Ltd. Emeishan Sub branch Pledgor: EMEISHAN TONGHUI PHARMACEUTICAL Co.,Ltd. Registration number: Y2023980030394 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right |