CN105738506B - A kind of measure the method for degradation impurity in orlistat capsule - Google Patents
A kind of measure the method for degradation impurity in orlistat capsule Download PDFInfo
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- G—PHYSICS
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- 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
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Abstract
A kind of measure the method for degradation impurity in orlistat capsule, relate to analytical chemistry field, described method uses high performance liquid chromatography, impurity mixes reference substance solution and sample solution injects high performance liquid chromatograph, complete the mensuration of degradation impurity in orlistat capsule；Described chromatographic condition is: chromatographic column: the chromatographic column with silica gel medicine ball granule as filler；Flowing phase: mobile phase A is acidic aqueous solution, and Mobile phase B is organic solvent, the percent by volume of mobile phase A and the percent by volume of Mobile phase B and remain 100%, carry out linear gradient elution.The method of the present invention uses Cortecs C18 (Waters, 150 × 4.6mm, 2.7 μm) chromatographic column, by eluent gradient elution program is optimized, can realize separating under same chromatographic condition by the process contaminants being difficult to separate near all of degradation impurity and main peak, can effectively detect degradation impurity described in orlistat capsule.
Description
Technical field
The present invention relates to analytical chemistry field, be specifically related to a kind of conventional high efficiency liquid chromatography for separating and determining orlistat
The method of degradation impurity in capsule.
Background technology
Orlistat found first in 1987, and orlistat (Orlistat) chemistry is entitled: (s)-2-first phthalein amino-4-
[[(2s, 3s)-3-hexyl-4-oxygen-2oxetany] methyl-dodecanoic ester, its chemical formula is as follows for methvl-pentanoic acid (s)-1-.Commodity
Entitled orlistat (Xenical), is the research and development of Hoffmann-La Roche company of Switzerland, and went up first in New Zealand in 1998
City, lists for 1999 in the U.S..Owing to orlistat is as a kind of potent, long acting gastrointestinal lipase inhibitor, it is a kind of non-
General action, the novel slimming medicine with well tolerable property and effectiveness.Obesity is treated, for fertilizer without appetite suppressant
The Drug therapy of fat disease opens new way.
The degradation impurity of orlistat mainly has following two to originate: one is that orlistat raw material and preparation are in production process
In, production technology degradation impurity can be produced；Two is orlistat capsule during stability is preserved owing to the impact of environment can be produced
Raw degradation impurity.These degradation impurity influence whether purity and the quality of medicine, need the analysis method setting up degradation impurity
Control the content of these degradation impurity.Title and the chemical structural formula of each degradation impurity are as follows:
In existing technology, 37 editions pharmacopeia of American Pharmacopeia (USP) provide the impurity analysis method of orlistat capsule,
But finding through research, when using the analysis method detection recorded in 37 editions pharmacopeia of USP, ring-opening product methyl ester is complete with orlistat
Full weight is folded, and the process contaminants close to main peak also cannot separate with main peak.It addition, in the document published, see " medicine
Learn journal ", volume 49 the 3rd phase, page 380～384 (2014) and " Journal of chromatography A " 1116 (2006),
Page 153～15.The orlistat capsule impurity analysis method delivered in these lists of references, all cannot efficiently separate in the present invention
The degradation impurity mentioned.
Summary of the invention
For above-mentioned technical problem, the present invention provides a kind of and measures the method for degradation impurity in orlistat capsule, and it is special
Levy and be: described method uses high performance liquid chromatography, impurity is mixed reference substance solution and sample solution injects efficient liquid phase
Chromatograph, completes the mensuration of degradation impurity in orlistat capsule；
Described chromatographic condition is: chromatographic column: the chromatographic column with silica gel medicine ball granule as filler；Flowing phase: mobile phase A is
Acidic aqueous solution, Mobile phase B is organic solvent, the percent by volume of mobile phase A and the percent by volume of Mobile phase B and all the time
Remain 100%, carry out linear gradient elution.Described chromatographic column preferred waters company Cortecs C18 post.
Further, described linear gradient is as follows: the original ratio of Mobile phase B be volume ratio 81～83%, keep
Rise to volume ratio 91% when 16min, 19min, keep 3min, rise to volume ratio 95% during 23min, keep 6min, drop during 30min
To volume ratio 81～83%, keep 7min.
Specifically, the solute of described mobile phase A is phosphoric acid or perchloric acid, and percent by volume is 0.005～0.025%；Institute
State Mobile phase B one or two kinds of thing mixed above in methanol, acetonitrile, ethanol, oxolane.Described mobile phase A
Solute solute is preferably phosphoric acid, and percent by volume is for selecting 0.01%～0.1%, most preferably 0.025%.Described Mobile phase B is preferred
For methanol or acetonitrile, more preferably acetonitrile.
Specifically, the flow velocity of described flowing phase is 0.5mL/min～2.0mL/min.It is preferably 1.3mL/min.
Specifically, described chromatogram column temperature is 25 DEG C～40 DEG C.It is preferably 35 DEG C.
Specifically, described method also includes detecting wavelength, and described detection wavelength is 190nm～205nm.It is preferably 195nm.
Specifically, described method also includes that sample size, described sample size are 10 μ L～50 μ L.
Specifically, described sample solution preparation method is as follows: takes orlistat capsule sample appropriate, by percent by volume is
The acetonitrile solution of 80% dissolves and dilutes, and is configured to every 1mL sample solution containing orlistat 0.5～1.5mg.
Specifically, described impurity mixing reference substance solution preparation method is as follows: take orlistat raw material, adds acetonitrile-water
Volume ratio be 4: 1 mixed solution make every 1mL containing the orlistat material storage liquid of 0.5mg, take impurity ring-opening product respectively different
Structure body, ring-opening product, impurity D, hexyl hendecanone and heneicosyl leucine impurity reference substance are appropriate, take destruction solution and fit
Amount, adds the mixed solution dilution that acetonitrile-water volume ratio is 4: 1, makes every 1mL impurity reference substance stock solution containing 0.5mg, measure
Above-mentioned impurity reference substance stock solution 1mL, puts in 50mL measuring bottle, is diluted to scale with orlistat material storage liquid, to obtain final product；Described
Destroy solution and destroy orlistat capsule sample by acid, alkali, oxygen, high temperature and illumination, the sample after destroying is added methanol-water body
Long-pending than being the mixed solvent ultrasonic dissolution of 4: 1 and diluting prepared.
Method of separating and assaying of the present invention, can realize in accordance with the following methods:
(1). instrument and experiment condition: the model of high performance liquid chromatograph, have no special requirements, the chromatograph that the present invention uses
Instrument for Shimadzu Corporation: LC-16, chromatographic column: Cortecs C18 (purchased from Waters, 150 × 4.6mm, 2.7 μm), flow phase
A be percent by volume be 0.025% phosphate aqueous solution, Mobile phase B is acetonitrile solution；Linear gradient elution is carried out by table 1；Arrange
Flowing phase flow velocity be 0.5mL/min～2.0mL/min, detection wavelength be 190nm～205nm, chromatogram column temperature be 25 DEG C～
40 DEG C, sampling volume 20 μ l.Wherein flow velocity is preferably 1.3mL/min；Column temperature preferably 35 DEG C；The detection preferred 195nm of wavelength.
<table 1>
(2). sample solution: take orlistat capsule sample appropriate, by the acetonitrile sample dissolution that percent by volume is 80%,
It is configured to every 1mL sample solution containing orlistat 0.5mg～1.5mg.
(3). the preparation of destruction solution:
1.. orlistat storing solution: take orlistat capsule 's content powder appropriate, adding acetonitrile-water volume ratio is 4: 1
Mixed solution make the solution of 0.5mg/mL, to obtain final product.
2.. hydrochloric acid methanol destroys solution: take orlistat capsule 's content powder appropriate, be equivalent to orlistat 45～
55mg, puts in 100mL measuring bottle, adds the mixed solution of methanol-water volume ratio 4: 1, ultrasonic and shake, and makes orlistat the most molten
Solve, add 0.1mol/L hydrochloric acid 5mL, after ambient temperatare puts 1 hour, add 0.1mol/L sodium hydroxide solution 5mL and neutralize, use first
The long-pending mixed solution mixed solvent than 4: 1 of alcohol-water is diluted to scale, to obtain final product.
3.. acidic alcohol destroys solution: take orlistat capsule 's content powder appropriate, be equivalent to orlistat 45～
55mg, puts in 100mL measuring bottle, adds the ethanol solution that percent by volume is 95%, ultrasonic and shake, and makes orlistat the most molten
Solve, add 0.1mol/L hydrochloric acid 5mL, after ambient temperatare puts 1 hour, add 0.1mol/L sodium hydroxide solution 5mL and neutralize, use body
Long-pending percentage ratio be 95% ethanol solution be diluted to scale, to obtain final product.
4.. sodium hydroxide methanol destroys solution: takes orlistat capsule 's content powder appropriate, is equivalent to orlistat 45
～55mg, put in 100mL measuring bottle, add the mixed solution of proper amount of methanol-water volume ratio 4: 1, ultrasonic and shake, make orlistat complete
CL, adds 0.1mol/L sodium hydroxide solution 5mL, after ambient temperatare puts 5 minutes, adds 0.1mol/L hydrochloric acid 5mL and neutralizes,
It is diluted to scale with the mixed solution mixed solvent of methanol-water volume ratio 4: 1, to obtain final product.
5.. sodium hydroxide ethanol destroys solution: takes orlistat capsule 's content powder appropriate, is equivalent to orlistat 45
～55mg, put in 100mL measuring bottle, add the ethanol solution that percent by volume is 95%, ultrasonic and shake, make orlistat the most molten
Solve, add 0.1mol/L sodium hydroxide solution 5mL, after ambient temperatare puts 5 minutes, add 0.1mol/L hydrochloric acid 5mL and neutralize, use body
Long-pending percentage ratio be 95% ethanol solution be diluted to scale, to obtain final product.
6.. Oxidative demage solution: take described storing solution 1mL, mass percent is the H of 30%2O2Solution 1mL to 10mL measures
In Ping, add the mixed solution that acetonitrile-water volume ratio is 4: 1 after mix homogeneously and be diluted to scale, place 30 minutes, to obtain final product.
7.. high temperature solution: take orlistat capsule sample appropriate, in 60 DEG C of baking ovens, place 3h, cool down after taking-up
To room temperature, add the mixed solution that acetonitrile-water volume ratio is 4: 1 and make the solution of 0.5mg/mL and get final product.
8.. illumination destroys solution: taking orlistat capsule sample appropriate, illumination 10 days under 5000 ± 500LX, after taking-up
Take the mixed solution that appropriate destruction sample addition acetonitrile-water volume ratio is 4: 1 make the solution of 0.5mg/mL and get final product.
(4). impurity mixing reference substance solution: take impurity ring-opening product isomer, ring-opening product, impurity D, hexyl hendecane respectively
Ketone and heneicosyl leucine impurity reference substance in right amount, preferably 0.5～1mg, take described destruction solution each 1mL appropriate, preferred,
To 50mL measuring bottle, add the mixed solution that acetonitrile-water volume ratio is 4: 1 and be diluted to scale, make impurity reference substance stock solution.Amount
Take above-mentioned impurity reference substance stock solution 1mL, put in 50mL measuring bottle, be diluted to scale with orlistat material storage liquid, to obtain final product.
(5). take the sample solution each 10 μ L～50 μ L prepared in the impurity mixing reference substance solution and (2) prepared in (4),
Described in (1), under chromatographic condition, inject chromatograph of liquid, observe chromatogram, complete the separation of orlistat capsule degradation impurity
Measure.
In all impurity, ring-opening product isomer (numbering: Z1): degraded produces under high temperature, oxidation and illumination condition；Open loop
Thing (numbering: Z2): be easily generated under oxidative conditions；Impurity D (numbering: Z4) (number: Z9): at height with heneicosyl leucine
It is easily generated under the conditions of temperature；Ring-opening product isomer methyl ester and ring-opening product methyl ester (numbering: Z3 and Z5): at sour or alkali and the dual work of methanol
Produce with lower generation or under methanol and high temperature dual function；Ring-opening product isomer ethyl ester and ring-opening product ethyl ester (numbering: Z6
And Z7): produce under acid or alkali and ethanol dual function or produce under ethanol and high temperature dual function；Hexyl hendecane
Ketone (numbering: Z8): degraded produces under the conditions of acid or alkalescence.Owing to ring-opening product isomer methyl ester, ring-opening product methyl ester, ring-opening product are different
Structure body ethyl ester and ring-opening product ethyl ester can only prepare by destroying, and therefore the configuration process of impurity reference substance solution had both used impurity pair
Also destruction solution is used according to product.
Compared with prior art, the method for the present invention uses Cortecs C18 (Waters, 150 × 4.6mm, 2.7 μm) color
Spectrum post, by being optimized eluent gradient elution program, can will be difficult to separation near all of degradation impurity and main peak
Process contaminants realizes separating under same chromatographic condition, can effectively detect degradation impurity described in orlistat capsule, solve Austria
The separation determination problem of degradation impurity in Li Sita capsule.This method specificity is strong, accuracy is high, easy to operate, the operation time
Short, ensure that the quality controllable of orlistat capsule.
In order to be more fully understood that and implement, describe the present invention below in conjunction with the accompanying drawings in detail.
Accompanying drawing explanation
Fig. 1 be embodiment 1 acetonitrile-water volume ratio be the high-efficient liquid phase chromatogram of the mixed solution of 4: 1；
Fig. 2 is that embodiment 1 orlistat impurity mixes reference substance solution high-efficient liquid phase chromatogram；
Fig. 3 is that embodiment 2 orlistat impurity mixes reference substance solution high-efficient liquid phase chromatogram；
Fig. 4 is the system suitability high-efficient liquid phase chromatogram of embodiment 3；
Fig. 5 is that embodiment 3 orlistat capsule sample measures high-efficient liquid phase chromatogram；
Fig. 6 is the system suitability high-efficient liquid phase chromatogram of embodiment 4；
Fig. 7 is that embodiment 4 orlistat capsule sample measures high-efficient liquid phase chromatogram；.
Detailed description of the invention
The preparation of destruction solution:
1.. orlistat storing solution: take orlistat capsule 's content powder appropriate, adding acetonitrile-water volume ratio is 4: 1
Mixed solution make the solution of 0.5mg/mL, to obtain final product.
2.. hydrochloric acid methanol destroys solution: takes orlistat capsule 's content powder appropriate, is equivalent to orlistat 50mg,
Put in 100mL measuring bottle, add the mixed solution of methanol-water volume ratio 4: 1, ultrasonic and shake, make orlistat be completely dissolved, add
0.1mol/L hydrochloric acid 5mL, after ambient temperatare puts 1 hour, adds 0.1mol/L sodium hydroxide solution 5mL and neutralizes, use methanol-water body
The long-pending mixed solution mixed solvent than 4: 1 is diluted to scale, to obtain final product.
3.. acidic alcohol destroys solution: takes orlistat capsule 's content powder appropriate, is equivalent to orlistat 50mg,
Put in 100mL measuring bottle, add the ethanol solution that percent by volume is 95%, ultrasonic and shake, make orlistat be completely dissolved, add
0.1mol/L hydrochloric acid 5mL, after ambient temperatare puts 1 hour, adds 0.1mol/L sodium hydroxide solution 5mL and neutralizes, use volume basis
It is diluted to scale than the ethanol solution being 95%, to obtain final product.
4.. sodium hydroxide methanol destroys solution: takes orlistat capsule 's content powder appropriate, is equivalent to orlistat
50mg, puts in 100mL measuring bottle, adds the mixed solution of proper amount of methanol-water volume ratio 4: 1, ultrasonic and shake, and makes orlistat complete
Dissolve, add 0.1mol/L sodium hydroxide solution 5mL, after ambient temperatare puts 5 minutes, add 0.1mol/L hydrochloric acid 5mL and neutralize, use
The mixed solution mixed solvent of methanol-water volume ratio 4: 1 is diluted to scale, to obtain final product.
5.. sodium hydroxide ethanol destroys solution: takes orlistat capsule 's content powder appropriate, is equivalent to orlistat
50mg, puts in 100mL measuring bottle, adds the ethanol solution that percent by volume is 95%, ultrasonic and shake, and makes orlistat the most molten
Solve, add 0.1mol/L sodium hydroxide solution 5mL, after ambient temperatare puts 5 minutes, add 0.1mol/L hydrochloric acid 5mL and neutralize, use body
Long-pending percentage ratio be 95% ethanol solution be diluted to scale, to obtain final product.
6.. Oxidative demage solution: take described storing solution 1mL, mass percent is the H of 30%2O2Solution 1mL to 10mL measures
In Ping, add the mixed solution that acetonitrile-water volume ratio is 4: 1 after mix homogeneously and be diluted to scale, place 30 minutes, to obtain final product.
7.. high temperature solution: take orlistat capsule sample appropriate, in 60 DEG C of baking ovens, place 3h, cool down after taking-up
To room temperature, add the mixed solution that acetonitrile-water volume ratio is 4: 1 and make the solution of 0.5mg/mL and get final product.
8.. illumination destroys solution: taking orlistat capsule sample appropriate, illumination 10 days under 5000 ± 500LX, after taking-up
Take the mixed solution that appropriate destruction sample addition acetonitrile-water volume ratio is 4: 1 make the solution of 0.5mg/mL and get final product.
Impurity mixing reference substance solution: take respectively impurity ring-opening product isomer, ring-opening product, impurity D, hexyl hendecanone and
Heneicosyl leucine impurity reference substance 0.5mg, takes described each destruction solution 1mL, to 50mL measuring bottle, adds acetonitrile-water body
Long-pending than be 4: 1 mixed solution be diluted to scale, make impurity reference substance stock solution a.Measure described impurity reference substance stock solution
A1mL, puts in 50mL measuring bottle, is diluted to scale with orlistat material storage liquid, to obtain final product.
Embodiment 1: system suitability
Instrument and experiment condition:
High performance liquid chromatograph: Shimadzu LC-16；
Chromatographic column: Cortecs C 18 (Waters, 150 × 4.6mm, 2.7 μm)；
Mobile phase A be percent by volume be 0.025% phosphate aqueous solution, Mobile phase B is acetonitrile；Wash by table 2 linear gradient
De-.
<table 2>
Flow velocity is 1.3mL/min；
Column temperature 35 DEG C；
Detection wavelength 195nm；
Sampling volume 20 μ l.
Experimental procedure:
Take the mixed solution that acetonitrile-water volume ratio is 4: 1 respectively and mix reference substance solution with impurity, by above-mentioned experiment condition
Carrying out efficient liquid phase chromatographic analysis, record chromatogram, result is shown in Fig. 1, Fig. 2, and in figure, ORL represents orlistat.It Fig. 2 is profit difficult to understand
Take charge of the chromatogram that he is corresponding with each degradation impurity, by table 3 and Fig. 2 it can be seen that orlistat and other each degradation impurity energy
Enough reach baseline separation, meet impurity determination requirement.
<table 3: the present embodiment analyzes method measurement result>
Embodiment 2: system suitability contrast test (USP37 method)
Instrument and experiment condition:
High performance liquid chromatograph: Shimadzu LC-16；
Chromatographic column: Nova-pak C18 (3.9mm × 150mm, 4.0 μm)；
Flowing phase: acetonitrile-phosphoric acid-water volume ratio is the mixed solution of 88: 0.05: 12；
Flow velocity: 1.0mL/min；
Column temperature: 35 DEG C；
Wavelength: 195nm；
Sample size: 20 μ l.
Experimental procedure:
Take impurity mixing reference substance solution, carry out efficient liquid phase chromatographic analysis by above-mentioned experiment condition, record chromatogram, knot
Fruit sees Fig. 3 and Biao 4, it is found that in the method that American Pharmacopeia is 37 editions, orlistat and ring-opening product methyl ester are entirely without separating, and
And each impurity goes out peak and is closer to, it is unfavorable for separating.Therefore, the method for American Pharmacopeia 37 editions is not suitable for the relevant thing of this product
Quality detection.
<37 editions standards of pharmacopoeia of table 4:USP analyze method measurement result>
Embodiment 1 is the most relatively, it can be deduced that, the impurity content of analysis method disclosed by the invention detection is equal
Higher than the impurity content of USP37 standard method detection, it is shown in Table 5；The operation time of analysis method the most disclosed by the invention is the lowest
Analysis method in USP 37.
<table 5:USP37 standard method of analysis detects Comparative result with from construction method impurity>
Embodiment 3
Instrument and experiment condition:
High performance liquid chromatograph: Agilent 1200；
Chromatographic column: Cortecs C 18 (Waters, 150 × 4.6mm, 2.7 μm)；
Mobile phase A be percent by volume be 0.005% phosphate aqueous solution, Mobile phase B is acetonitrile；Wash by table 6 linear gradient
De-.
<table 6>
Flow velocity is 1.25mL/min；
Column temperature 40 DEG C；
Detection wavelength 195nm；
Sampling volume 20 μ l.
Experimental procedure:
Orlistat capsule sample solution: take orlistat capsule 's content 105mg, puts in 100mL measuring bottle, with volume hundred
Proportion by subtraction be 80% acetonitrile solution dissolve and be diluted to scale, make sample solution.
Impurity mixing reference substance solution in the present embodiment: take impurity ring-opening product isomer, ring-opening product, impurity D, hexyl respectively
Hendecanone and heneicosyl leucine impurity reference substance 0.5mg, remove acidic alcohol and destroy solution and sodium hydroxide ethanol
Destroy other the described each 1mL of destruction solution outside solution, to 50mL measuring bottle, add the mixed solution that acetonitrile-water volume ratio is 4: 1
It is diluted to scale, makes impurity reference substance stock solution b.Measure described impurity reference substance stock solution b 1mL, put in 50mL measuring bottle,
It is diluted to scale with described orlistat material storage liquid, to obtain final product.
Take impurity mixing reference substance solution and orlistat capsule sample solution in the present embodiment respectively, by above-mentioned experiment bar
Part carries out efficient liquid phase chromatographic analysis, records chromatogram, and result is shown in Fig. 4～5 and table 7～8.From result, system suitability
In collection of illustrative plates, between each peak, separating degree is all higher than 1.5, on the premise of meeting system suitability, in sample survey orlistat peak with
Other impurities peak separates good, can meet mensuration requirement.
<table 7 system suitability result detector: 195nm>
<table 8 assay detector: 195nm>
Embodiment 4
Instrument and experiment condition:
High performance liquid chromatograph: Shimadzu LC-16；
Chromatographic column: Cortecs C18 (Waters, 150 × 4.6mm, 2.7 μm)；
Mobile phase A be percent by volume be 0.025% phosphate aqueous solution, Mobile phase B is acetonitrile；Wash by table 9 linear gradient
De-.
<table 9>
Flow velocity is 1.25mL/min；
Column temperature 30 DEG C；
Detection wavelength 195nm；
Sampling volume 20 μ l.
Experimental procedure: take orlistat capsule 's content 105mg, puts in 100mL measuring bottle, is 80% by percent by volume
Acetonitrile solution dissolves and is diluted to scale, prepares sample solution.Impurity mixing reference substance solution and this reality in Example 3 respectively
Execute the orlistat capsule sample solution in example, carry out efficient liquid phase chromatographic analysis by above-mentioned experiment condition, record chromatogram, knot
Fruit sees Fig. 6～7 and table 10～11.From result, in system suitability collection of illustrative plates, between each peak, separating degree is all higher than 1.5, full
On the premise of the pedal system suitability, in sample survey, orlistat peak separates well with other impurities peak, can meet mensuration requirement.
<table 10 system suitability result detector: 195nm>
<table 11 assay detector: 195nm>
Knowable to experimental result, degradation impurity disclosed by the invention analyzes method, can be by orlistat and other fall
Solve separated from impurities, it is possible to the content of each degradation impurity of Accurate Determining, thus efficiently control the product of orlistat
Quality.
The invention is not limited in above-mentioned embodiment, if various changes or deformation to the present invention are without departing from the present invention
Spirit and scope, if these are changed and within the scope of deformation belongs to claim and the equivalent technologies of the present invention, then this
Bright being also intended to comprises these changes and deformation.
Claims (7)
1. one kind measures the method for degradation impurity in orlistat capsule, it is characterised in that: described method uses high-efficient liquid phase color
Spectrometry, mixes reference substance solution by impurity and sample solution injects high performance liquid chromatograph, completes to degrade in orlistat capsule
The mensuration of impurity；
Described chromatographic condition is:
Chromatographic column: the chromatographic column with silica gel medicine ball granule as filler；
Flowing phase: mobile phase A is acidic aqueous solution, and Mobile phase B is organic solvent, the percent by volume of mobile phase A and Mobile phase B
Percent by volume and remain 100%, carry out linear gradient elution；The original ratio of Mobile phase B be volume ratio 81 ~
83%, keep 16min, rise to volume ratio 91% during 19min, keep 3min, rise to volume ratio 95% during 23min, keep 6min,
It is down to volume ratio 81 ~ 83% during 30min, keeps 7min；
Described mobile phase A be percent by volume be 0.025% phosphate aqueous solution, Mobile phase B is acetonitrile.
Method the most according to claim 1, it is characterised in that: the flow velocity of described flowing phase is 0.5mL/min ~ 2.0mL/
min。
Method the most according to claim 1, it is characterised in that: described chromatogram column temperature is 25 DEG C ~ 40 DEG C.
Method the most according to claim 1, it is characterised in that: described method also includes detecting wavelength, described detection wavelength
For 190nm ~ 205nm.
Method the most according to claim 1, it is characterised in that: described method also includes that sample size, described sample size are 10 μ
L ~50μL。
Method the most according to claim 1, it is characterised in that described sample solution preparation method is as follows: take orlistat glue
Capsule sample, dissolves with the acetonitrile solution that percent by volume is 80% and dilutes, and is configured to every 1mL 0.5 ~ 1.5mg Han orlistat
Sample solution.
Method the most according to claim 1, it is characterised in that described impurity mixing reference substance solution preparation method is as follows: take
Orlistat raw material, adds the mixed solution that acetonitrile-water volume ratio is 4:1 and makes every 1mL orlistat raw material storage containing 0.5mg
Standby liquid, takes impurity ring-opening product isomer, ring-opening product, impurity D, hexyl hendecanone and heneicosyl leucine impurity pair respectively
Appropriate according to product, take destruction solution appropriate, add the mixed solution dilution that acetonitrile-water volume ratio is 4:1, make impurity reference substance and stock
Liquid, measures described impurity reference substance stock solution 1mL, puts in 50mL measuring bottle, is diluted to scale i.e. with orlistat material storage liquid
?；Described destruction solution destroys orlistat capsule sample by acid, alkali, oxygen, high temperature and illumination, to the diluted sample after destroying
Prepare；Described impurity concrete structure formula is as follows:
,,,,。
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| CN109580850B (en) * | 2019-01-29 | 2021-09-17 | 杭州新博思生物医药有限公司 | High performance liquid chromatography method for separating and determining oseltamivir phosphate and specific impurities thereof |
| CN113834891B (en) * | 2021-11-26 | 2022-03-08 | 广州国标检验检测有限公司 | Method for detecting phenylphosphine compounds in medicine |
| CN114137120A (en) * | 2021-11-29 | 2022-03-04 | 赛诺神畅医疗科技有限公司 | Method for detecting related substances in rapamycin drug stent |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103788028A (en) * | 2012-10-31 | 2014-05-14 | 江苏汉邦科技有限公司 | Orlistat industrial liquid chromatogram preparation method |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103788028A (en) * | 2012-10-31 | 2014-05-14 | 江苏汉邦科技有限公司 | Orlistat industrial liquid chromatogram preparation method |
Non-Patent Citations (4)
| Title |
|---|
| Comparison of impurity profiles os Orlistat pharmaceutical products using HPLC tandem mass spectrometry;A Schneider等;《Jounal of Pharmaceutical&Biomedical Analysis》;20101102;第53卷(第3期);第767-772页 * |
| 减肥保健食品中奥利司他的HPLC-UV-ESI-MS的测定;肖松等;《卫生研究》;20060630;第35卷(第3期);第355-356页 * |
| 奥利司他中有关物质的UPLC-MA/MS研究;张婷婷等;《药学学报》;20140331;第49卷(第3期);第381页材料与方法部分 * |
| 奥利司他原料药制备过程中的杂质分析;石其德等;《中国药业》;20131120;第22卷(第22期);第13-15页 * |
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Address after: 528451 Guangdong province Zhongshan Nanlang town of Southern China modern Chinese Medicine City Branch Chong Park No. 2 Patentee after: Zhongshan Wan Han Pharmaceutical Co., Ltd. Address before: 528451 Guangdong province Zhongshan Nanlang town of Southern China modern Chinese Medicine City Branch Chong Park No. 2 Patentee before: Zhong Shanwanhan Pharmaceutical Technology Co., Ltd |
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Application publication date: 20160706 Assignee: Zhongshan Wan new drug research and Development Co., Ltd. Assignor: Zhongshan Wan Han Pharmaceutical Co., Ltd. Contract record no.: 2018440000015 Denomination of invention: Method for measuring degraded impurities in orlistat capsules Granted publication date: 20161102 License type: Common License Record date: 20180212 |