CN102478555A - Methyprednisolone aceponate and high performance liquid phase analysis method of its preparation - Google Patents
Methyprednisolone aceponate and high performance liquid phase analysis method of its preparation Download PDFInfo
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- CN102478555A CN102478555A CN2010105644399A CN201010564439A CN102478555A CN 102478555 A CN102478555 A CN 102478555A CN 2010105644399 A CN2010105644399 A CN 2010105644399A CN 201010564439 A CN201010564439 A CN 201010564439A CN 102478555 A CN102478555 A CN 102478555A
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Abstract
The invention relates to methyprednisolone aceponate and a high performance liquid phase analysis method of its preparation. In the invention, acetonitrile and water in a ratio of 40:60-70:30 are adopted as the mobile phases, and an ultraviolet detector is taken as the detector.
Description
Technical field:
The present invention relates to the high efficient liquid phase analysis method of a kind of Methylprednisolone Aceponate and preparation thereof.
Background technology:
(methyprednisolone aceponate is that German Schering AG is synthetic MPA) to be produced Methylprednisolone Aceponate, and commodity are called Advantan.Methylprednisolone Aceponate is a kind of of steroids; Can suppress the reaction of inflammation and allergic skin; The simultaneously also constrain symptom that adds the connected reaction of rapid regeneration with cell and cause; For example erythema, oedema, thickization of skin, coarse the going down of skin surface, and alleviate problems such as itch, burning heat sensation and pain.MPA metabolism conversion regime in vivo is MPA--6,2-methylprednisolone-21 propionic ester--6, the 2-methylprednisolone.More than these metabolic products all combine in vivo and lose intrinsic activity with glucuronic acid, thereby do not produce the influence of corticosteroid in vivo.Therefore external application can not cause the spinoff of whole body.Use the experiment of mouse ear and show, MPA suppresses the needed dosage of ultraviolet dermatitis than low many of the amount of other two kinds of corticosteroid formulations (hydrocortisone butyric ester, clobetasol) needs.Therefore MPA has antiinflammatory action.Research shows that the level of patient's blood plasma cortisol of external application MPA always is lower than normal value, the spinoff of this explanation external application MPA unsystematic.The MPA external application is a low atrophy group and the strong corticosteroid new drug of antiphlogistic effects.Tolerance is good after the MPA clinical practice, does not find systemic spinoff.Have only slight or moderate itch, erythema after the minority case local application, burn, drying and furfur, but do not find atrophoderma and telangiectasis.MPA is current leading external application corticosteroid formulations, and its curative effect is superior to known corticosteroid, and MPA is again the efficient corticosteroid of no halogen family group, and spinoff is light, is a kind of corticosteroid external preparation that can be used for children.
The chemistry of Methylprednisolone Aceponate is called 21-acetyl group-11 beta-hydroxy-6 Alpha-Methyl-17 α-propiono-1,4-pregnen diethylene-3, and 20-diketone, CASRN are 86401-95-8.
The Methylprednisolone Aceponate chemical structural formula
21 have acetate on the structure of Methylprednisolone Aceponate; 17 have propionic ester; The impurity of structure proximates such as 21-methylprednisolone acetate, 17-propionic acid methylprednisolone, 21-propionic acid methylprednisolone, 17-methylprednisolone acetate maybe or appear occurring in bulk drug; In the preparation storage process, be prone to take place the hydrolysis phenomenon of ester, cause main content to descend, related substance rises; Promptly there are material such as 21-methylprednisolone acetate, 17-propionic acid methylprednisolone after the hydrolysis, possibly have the material of transesterification such as the impurity of structure proximates such as 21-propionic acid methylprednisolone, 17-methylprednisolone acetate again.In order to confirm a kind of method that can Methylprednisolone Aceponate raw material and preparation thereof be carried out labor; The scientific research personnel has carried out continuous research, people such as Chen Kang report (test of the vinegar third methylprednisolone tranilast silicate gel film vitro release degree, Chinese medicine company; Rolled up 22 pages of the 10th phases in 2008 the 17th) can detect Methylprednisolone Aceponate in order to following method; Chromatographic column be Diamonsil C18 post (250mm * 4.6mm, 5m), moving phase is 0.02mol/L potassium hydrogen phosphate (pH=3.88)-acetonitrile (35: 65); Flow velocity is 1.2mL/min, and detecting wavelength vinegar third methylprednisolone is 244nm.Use phosphoric acid hydrogen potassium solution and the acetonitrile of pH=3.88 in the moving phase; Maximum problem is under acid condition; Methylprednisolone Aceponate is prone to take place the exchange of ester hydrolysis and 17 and 21 esters; In analytic process,, in analytic process, also can there be the problem of ester decomposition and transesterification owing to use acid moving phase.Coordinate and direct principle according to international working standard ICH three parts; Impurity for the content more than 0.2% need be identified structure, and the impurity more than 0.5% need carry out pharmacological evaluation, generally all is controlled at below 0.5% for the single impurity of bulk drug simultaneously; Just because the increase of the trace of the impurity content that analytical approach itself causes; All can make product quality receive bigger influence most probably, and even be judged as defectively, this type problem is particularly outstanding when exporting to the international market.On the other hand because buffer salt is prone to separate out, use salt buffer as moving phase before, salt buffer will filter earlier, wants purging system after using up, and to avoid separating out because of buffer salt instrument and filler is brought infringement, experimental implementation is more loaded down with trivial details.
Summary of the invention:
For the content, the impurity analysis that make Methylprednisolone Aceponate more accurate; Reduce analytical approach itself and influence impurity content; Constantly study through us; Surprised discovery can reduce the hydrolysis of Methylprednisolone Aceponate in analytic process in the moving phase of using pure water and acetonitrile, makes on the result of analysis more accurate.
We provide the high efficient liquid phase analysis method of a kind of Methylprednisolone Aceponate and preparation thereof, and its analytical approach is following:
It is the chromatographic column of filling agent that a chromatographic column is selected octadecylsilane chemically bonded silica for use
B is a moving phase with acetonitrile and water, and proportioning is an acetonitrile: water is between 40: 60 to 70: 30
C UV-detector wavelength is 230-250nm
D is according to the content of external standard method calculation sample;
Above-mentioned Methylprednisolone Aceponate preparation is preferably cream.More preferably this kind analytical approach is applicable to the analysis of Methylprednisolone Aceponate.
Described analytical approach, it is characterized in that the acetonitrile-water proportion of mobile phase is an acetonitrile: water is between 45: 55 to 60: 40, preferred acetonitrile-water proportion of mobile phase is an acetonitrile: water is between 50: 50 to 55: 45.More preferably the acetonitrile-water proportion of mobile phase is an acetonitrile: water is 55: 45.
The preferred 235-245nm of said UV-detector wavelength.240nm more preferably.
Analytical approach provided by the invention has been carried out mensuration means such as precision, detectability, all meets the respective specified of Chinese Pharmacopoeia version in 2005.In addition,, done the methodology checking that is at present, comprised system suitability test, linear test, recovery test and specificity test according to Chinese Pharmacopoeia version in 2005.Through these checkings, analytical approach provided by the invention is practical reliable, and stability better.
The high performance liquid chromatogram method of Methylprednisolone Aceponate provided by the invention and preparation thereof has following advantage:
(1) use common liquid chromatograph to get final product, equipment requirements is not high.
(2) moving phase two common being easy to get of medium of selecting for use, feasibility is high.
(3) operating process is simple and convenient.
(4) applicability is good, can be widely used in Methylprednisolone Aceponate and preparation thereof.
Description of drawings:
Fig. 1: the chromatogram of measuring according to the moving phase of embodiment 1
Fig. 2: the chromatogram of measuring according to the moving phase of embodiment 2
Fig. 3: the chromatogram of measuring according to the moving phase of embodiment 3
Fig. 4: the chromatogram of measuring according to the moving phase of embodiment 4
Fig. 5: the reference substance chromatogram in the detection of Methylprednisolone Aceponate emulsifiable paste
Fig. 6: Methylprednisolone Aceponate emulsifiable paste chromatogram.
Embodiment:
To do further description to the present invention through embodiment below, these descriptions are not that content of the present invention is done further to limit.
One skilled in the art will understand that to be equal to replacement to what technical characterictic of the present invention was done, or corresponding the improvement, still belong within protection scope of the present invention.
One, the detection of bulk drug
Chromatographic column: C18; 5 μ m; 4.6mm * 250mmAgilent post
Detect wavelength: 240nm
Flow velocity: 1.0ml/min
Instrument: CBM 20A island Tianjin 10AV
These article of getting are an amount of, accurate claim fixed, add the moving phase dissolving and quantitatively dilution process the solution that contains 0.5mg among every 1ml approximately, precision is measured 20 μ l and is injected liquid chromatograph, the record chromatogram; It is an amount of that other gets the Methylprednisolone Aceponate reference substance, and accurate the title decides, and measures with method., promptly get with calculated by peak area by external standard method.
| Chromatographic condition | Moving phase | The main peak retention time | Degree of separation |
| Embodiment 1 | Acetonitrile: water=45: 55 | 22.773min | 7.8 |
| Embodiment 2 | Acetonitrile: water=50: 50 | 18.217min | 7.2 |
| Embodiment 3 | Acetonitrile: water=55: 45 | 12.782min | 5.5 |
| Embodiment 4 | Acetonitrile: water=60: 40 | 9.732min | 4.3 |
Two, the detection of Methylprednisolone Aceponate emulsifiable paste
Chromatographic column: C18; 5 μ m; 4.6mm * 250mmAgilent post
Detect wavelength: 240nm flow velocity: 1.0ml/min moving phase: acetonitrile: water=55: 45
Instrument: No. 2 machines in Tianjin, CBM 20A island
These article of getting an amount of (being equivalent to Methylprednisolone Aceponate 2mg approximately), the accurate title, decide, and puts in the 50ml measuring bottle, adds the about 30ml of methyl alcohol; Put in 80 ℃ of water-baths and heated 2 minutes, jolting makes the Methylprednisolone Aceponate dissolving, puts and is chilled to room temperature, is diluted to scale with methyl alcohol; Shake up, put and cool off in the ice bath more than 1 hour, take out filtration rapidly; Put to room temperature, get filtrating 20 μ l and inject liquid chromatograph, the record chromatogram.It is an amount of that other gets the Methylprednisolone Aceponate reference substance, and accurate the title decides, and processes the solution that contains 0.04mg among every 1ml approximately with dissolve with methanol and quantitative dilution, measures with method, presses external standard method with calculated by peak area, promptly gets.
Detect according to the method described above, the result is following:
| |
5 |
| Content (%) | 97.7 |
Claims (9)
1. the high efficient liquid phase analysis method of Methylprednisolone Aceponate and preparation thereof is characterized in that moving phase is acetonitrile-water, and proportioning is an acetonitrile: water is between 40: 60 to 70: 30, and detecting device is a UV-detector.
2. analytical approach as claimed in claim 1 is characterized in that Methylprednisolone Aceponate is analyzed.
3. analytical approach as claimed in claim 1 is characterized in that the Methylprednisolone Aceponate preparation is a cream.
4. analytical approach as claimed in claim 1 is characterized in that the UV-detector wavelength is 230-250nm.
5. analytical approach as claimed in claim 1 is characterized in that the UV-detector wavelength is 235-245nm.
6. analytical approach as claimed in claim 1 is characterized in that the UV-detector wavelength is 240nm.
7. analytical approach as claimed in claim 1, it is characterized in that the acetonitrile-water proportion of mobile phase is an acetonitrile: water is between 45: 55 to 60: 40.
8. analytical approach as claimed in claim 1, it is characterized in that the acetonitrile-water proportion of mobile phase is an acetonitrile: water is between 50: 50 to 55: 45.
9. analytical approach as claimed in claim 1, it is characterized in that the acetonitrile-water proportion of mobile phase is an acetonitrile: water is 55: 45.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111380970A (en) * | 2018-12-29 | 2020-07-07 | 天津药业研究院有限公司 | Method for detecting content of methylprednisolone aceponate and related substances |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101468024A (en) * | 2007-12-27 | 2009-07-01 | 天津金耀集团有限公司 | Hormonic autacoid emulsifiable paste |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101468024A (en) * | 2007-12-27 | 2009-07-01 | 天津金耀集团有限公司 | Hormonic autacoid emulsifiable paste |
Non-Patent Citations (2)
| Title |
|---|
| 贾艺琦等: "高效液相色谱法测定醋酸泼尼松的有关物质", 《天津药学》 * |
| 项竟佐等: "RP-HPLC法测定帕利百中醋酸泼尼松龙的含量及其有关物质", 《药学服务与研究》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111380970A (en) * | 2018-12-29 | 2020-07-07 | 天津药业研究院有限公司 | Method for detecting content of methylprednisolone aceponate and related substances |
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Application publication date: 20120530 |