CN107870210A - The method for determining Li Gelieting contents in Li Gelieting bulk drugs - Google Patents
The method for determining Li Gelieting contents in Li Gelieting bulk drugs Download PDFInfo
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- CN107870210A CN107870210A CN201610862128.8A CN201610862128A CN107870210A CN 107870210 A CN107870210 A CN 107870210A CN 201610862128 A CN201610862128 A CN 201610862128A CN 107870210 A CN107870210 A CN 107870210A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
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Abstract
The method that the present invention proposes Li Gelieting contents in a kind of measure Li Gelieting bulk drugs, methods described include：The Li Gelieting bulk drugs are analyzed by HPLC analytical method, to obtain chromatogram；And based on the chromatogram, the content of Li Gelieting in the Li Gelieting bulk drugs is determined, wherein, the high performance liquid chromatography uses following condition：Chromatographic column is YMC PACK ODS AM, 4.6 × 250mm, 5 microns, detector DAD, Detection wavelength is 294nm, column temperature is 35 DEG C, and mobile phase A is mutually 10~50mmol/L potassium phosphate buffer, and the pH of the potassium phosphate buffer is 3.0~5.0, Mobile phase B is mutually acetonitrile, flow velocity is 1.0mL/min, elutes and uses isocratic elution, and the volume ratio of A phases and B phases is 72 in the isocratic elution:28, run time 10min.Using this method, can content that is easy, accurate, delicately, specificity determining Li Gelieting in Li Gelieting bulk drugs, so as to effectively control drug effect, quality and the pharmaceutical safety of Li Gelieting bulk drugs.
Description
Technical field
The present invention relates to biomedicine field, specifically, the present invention relates to Li Gelieting in measure Li Gelieting bulk drugs
The method of content.
Background technology
Type ii diabetes are due to body islet β cell insufficient insulin or target cell to insulin insensitivity (pancreas
Insulin resistance) caused by, also known as adult-onset diabetes.The more sequela at 35~40 years old of type ii diabetes, account for glycosuria
Patient more than 90%.
Li Gelieting (Linagliptin) is a kind of dipeptidyl peptidase-4 (DPP-4) inhibitor, is that one kind is used to treat
Effective medicine of type ii diabetes.Its molecular structure is：With methanol is soluble in, second is slightly soluble in
Nitrile, it is insoluble in the characteristic of water.
Li Gelieting content is to influence the key factor of Li Gelieting bulk drug drug effects in Li Gelieting bulk drugs, and
Assess the key index of Li Gelieting bulk drug pharmaceutical safeties.However, how effectively to determine Li Gelie in Li Gelieting bulk drugs
The content in spit of fland still needs further to be developed.
The content of the invention
It is contemplated that at least solves one of technical problem in correlation technique to a certain extent.Therefore, the present invention
One purpose is in a kind of method for proposing simplicity, accurately, delicately detecting Li Gelieting contents in Li Gelieting bulk drugs.
In the first aspect of the present invention, the present invention proposes Li Gelieting contents in a kind of measure Li Gelieting bulk drugs
Method, according to an embodiment of the invention, methods described include：It is former to the Li Gelieting by HPLC analytical method
Material medicine is analyzed, to obtain chromatogram；And based on the chromatogram, determine Li Gelie in the Li Gelieting bulk drugs
The content in spit of fland, wherein, the high performance liquid chromatography uses following condition：Chromatographic column is YMC-PACK ODS-AM, 4.6 ×
250mm, 5 microns, detector DAD, Detection wavelength 294nm, column temperature is 35 DEG C, and mobile phase A is mutually for 10~50mmol/L's
Potassium phosphate buffer, the pH of the potassium phosphate buffer is 3.0~5.0, and Mobile phase B is mutually acetonitrile, and flow velocity is
1.0mL/min, elute and use isocratic elution, the volume ratio of A phases and B phases is 72 in the isocratic elution：28, run time is
10min.Using detection method according to embodiments of the present invention, can it is easy, accurate, delicately, specificity determine Li Gelieting
Li Gelieting content in bulk drug, so as to effectively control drug effect, quality and the pharmaceutical safety of Li Gelieting bulk drugs.
According to an embodiment of the invention, the method for Li Gelieting contents can also be entered in said determination Li Gelieting bulk drugs
One step includes at least one following additional technical feature：
According to an embodiment of the invention, the pH of the potassium phosphate buffer is 4.0.Inventor has found in an experiment,
The pH of potassium phosphate buffer is that 4.0, Li Gelieting main peaks and impurity peaks existing forms are single, and peak separating degree is good, main peak shape
Separating effect sharp and that the reproduction of main peak retention time can be realized.
According to an embodiment of the invention, the mobile phase A is mutually 50mmol/L potassium phosphate buffer.Inventor is led to
Cross experiment to find, mobile phase A mutually uses 50mmol/L potassium phosphate buffer, the Li Gelieting small, peak shape of main peak hangover
It is good.
According to an embodiment of the invention, the Li Gelieting bulk drugs are provided in the form of need testing solution, wherein,
The need testing solution is potassium dihydrogen phosphate-acetonitrile solution of Li Gelieting bulk drugs, and is based on every milliliter of test sample
Solution, the content of Li Gelieting bulk drugs is 0.2mg, wherein, the potassium dihydrogen phosphate-acetonitrile solution is the A phase and B phases
Mixed solution, the volume ratio of the A phases and B phases is 72：28.The sample introduction concentration of Li Gelieting bulk drugs is in 0.2mg/mL, both
Detection sensitivity good enough can be ensured, ensure that Li Gelieting main peaks do not deform, not in the linear of UV because concentration is overloaded
In response range, it is ensured that do not cause the deformation of UV spectrums to cause the purity factor unqualified because of excessive concentration.
According to an embodiment of the invention, the dosage of the need testing solution is 10 microlitres.According to an embodiment of the invention, supply
The dosage of test sample solution is 10 microlitres, it is ensured that more true, reliable, accurate to the measure of Li Gelieting contents.
According to an embodiment of the invention, the HPLC analytical method uses standard control solution, the standard
Contrast solution is potassium dihydrogen phosphate-acetonitrile solution of Li Gelieting standard items, and is based on every milliliter of standard control solution,
The quality of Li Gelieting standard items is 0.2mg.Standard control solution is prepared according to need testing solution, so as to higher special
Li Gelieting content in attribute rapid and accurate determination Li Gelieting bulk drugs.
According to an embodiment of the invention, it is described to be based on the chromatogram, determine Li Gelie in the Li Gelieting bulk drugs
The content in spit of fland is determined by below equation：
Wherein, WS1For the quality of Li Gelieting standard items in standard control solution；ATFor Li Gelieting in need testing solution
Main peak peak area；DTFor the extension rate of need testing solution；AS1For Li Gelieting main peak peak areas in standard control solution；DS1For
The extension rate of standard control solution；WTFor the quality of Li Gelieting bulk drugs in need testing solution；P is Li Gelieting standard items
Purity；W is the content of moisture in Li Gelieting bulk drugs.According to an embodiment of the invention, sharp lattice are determined using aforesaid way
The content of Li Gelieting in the bulk drug of spit of fland is arranged, accuracy rate is high, as a result more true and reliable.
In the second aspect of the present invention, the present invention proposes Li Gelieting contents in a kind of measure Li Gelieting bulk drugs
Method, according to an embodiment of the invention, methods described include：
(1) chromatographic condition
Chromatographic column is YMC-PACK ODS-AM, 4.6 × 250mm, 5 micron,
Detector is DAD,
Detection wavelength is 294nm,
Column temperature is 35 DEG C,
Mobile phase A is mutually 50mmol/L potassium phosphate buffer, and the pH of the potassium phosphate buffer is 4.0,
Mobile phase B is mutually acetonitrile,
Flow velocity is 1.0mL/min,
Elute and use isocratic elution, the volume ratio of A phases and B phases is 72 in the isocratic elution:28,
Run time is 10min,
(2) blank solution is prepared
The volume ratio of A phases and B phases is 72：28 mixed solution as the blank solution,
(3) need testing solution is prepared
Accurately weighed Li Gelieting bulk drugs 20mg, puts in 100mL volumetric flasks, is dissolved with blank solution, and does ultrasonic place
Reason, is diluted to scale, shakes up, produce the need testing solution,
(4) standard control solution is prepared
Accurately weighed Li Gelieting standard items 20mg, puts in 100mL volumetric flasks, is dissolved with blank solution, and does ultrasonic place
Reason, is diluted to scale, shakes up, produce the standard control solution,
(5) by 10 microlitres of need testing solution injecting chromatographs, chromatogram is obtained, is calculated according to the chromatogram for examination
Li Gelieting content in product solution,
Wherein, the content of Li Gelieting in need testing solution is calculated as follows, takes the average value of 2 measurement results to make
For measurement result：
In formula, WS1For Li Gelieting standard items quality in standard control solution；
ATFor the average value of Li Gelieting main peaks peak area in need testing solution；
DTFor the extension rate of need testing solution；
AS1For the average value of Li Gelieting main peak peak areas in each 2 pin standard control solution before and after need testing solution；
DS1For the extension rate of standard control solution；
WTFor the quality of Li Gelieting bulk drugs in need testing solution；
P is the purity of Li Gelieting standard items；
W is the content of moisture in Li Gelieting bulk drugs；
The dosage of 1 pin standard control solution is 10 microlitres.
Using detection method according to embodiments of the present invention, Li Gelieting can be determined to easy, accurate, sensitive, specificity
Li Gelieting content in bulk drug, so as to effectively control drug effect, quality and the pharmaceutical safety of Li Gelieting bulk drugs.
Brief description of the drawings
Fig. 1 is according to embodiments of the present invention 1 Li Gelieting HPLC-DAD ultraviolet spectrograms；
Fig. 2 is according to embodiments of the present invention 1 chromatogram of the Li Gelieting bulk drugs under 226nm and 294nm；
Fig. 3 be according to embodiments of the present invention 1 Li Gelieting bulk drugs pH=4.0 10mM potassium dihydrogen phosphates buffer it is molten
Liquid is as the chromatogram under mobile phase and isocratic condition；
Fig. 4 be according to embodiments of the present invention 1 Li Gelieting bulk drugs pH=4.0 50mM potassium dihydrogen phosphates buffer it is molten
Liquid is as the chromatogram under mobile phase；
Fig. 5 is according to embodiments of the present invention 2 blank solution chromatogram；
Fig. 6 is the chromatogram of according to embodiments of the present invention 2 standard control solution；And
Fig. 7 is according to embodiments of the present invention 2 need testing solution chromatogram.
Embodiment
Embodiments of the invention are described below in detail.The embodiments described below is exemplary, is only used for explaining this hair
It is bright, and be not considered as limiting the invention.Unreceipted particular technique or condition in embodiment, according to text in the art
Offer described technology or condition or carried out according to product description.Agents useful for same or the unreceipted production firm person of instrument,
For the conventional products of acquisition purchased in market can be passed through.
Embodiment 1
In embodiments of the present invention, inventor describes the side of Li Gelieting contents in measure Li Gelieting bulk drugs in detail
The development process of method.
The determination of 1.1 Detection wavelengths
HPLC-DAD ultraviolet spectrograms show that main peak Li Gelieting has characteristic absorption peak in 226nm, 294nm, as a result as schemed
Shown in 1.But under the conditions of 226nm, the quantity of impurity peaks is more, as a result as shown in Figure 2.In order to reduce the dry of impurity peaks as far as possible
Disturb, inventor carries out content analysis method exploitation from the second absorbing wavelength 294nm.
1.2 types of elution are screened
On the basis of inventor researches and develops (method of impurity content in measure Li Gelieting bulk drugs) early stage in this laboratory,
Inventor has carried out to screen further to type of elution, to determine to determine the side of Li Gelieting contents in Li Gelieting bulk drugs
Method, inventor have found that under conditions of isocratic elution, than gradient elution, Li Gelieting can be eluted out in a short time,
And Li Gelieting polarity is larger, retain on anti-phase weak.Specific detection chromatographic condition is as described below：
Chromatographic column：YMC-Pack ODS-AM 250*4.6mm, 5 microns；
Detection wavelength：294nm；
Flow velocity：1.0mL/min；
Column temperature：35℃；
Mobile phase：A phases are that (compound method is 10mM pH=4.0 potassium dihydrogen phosphate buffer solutions：Weigh 1.4g di(2-ethylhexyl)phosphates
Hydrogen potassium, add 1L ultra-pure waters to dissolve, adjust pH to 4.0 with phosphoric acid, filtered with 0.45 micron membrane filter, deaerate and produce)；
B phases are acetonitrile；
Sample size：10 microlitres；
Run time：10min；
Solution is prepared：Li Gelieting bulk drugs about 20mg is taken, it is accurately weighed, put in 100mL volumetric flasks, with diluent (A phases
Volume ratio with B phases is 72：28 mixed solution) make dissolving in right amount and be diluted to scale, shake up, produce；
Isocratic elution：A phases：B phase=72：28.
Under these conditions, chromatogram is obtained as shown in figure 3, main peak retention time is about 7.10min, and symmetrical factor is about
2.3 peak height about 420mAU.
The determination of 1.3 mobile phases
On the basis of inventor researches and develops (method of impurity content in measure Li Gelieting bulk drugs) early stage in this laboratory,
Carry out to screen further to the concentration of the potassium dihydrogen phosphate of mobile phase, to determine in optimal measure Li Gelieting bulk drugs
The method of Li Gelieting contents.
Fig. 3 results are shown, using pH=4.0 10mM potassium dihydrogen phosphate buffer solutions, the symmetrical factor of main peak is 2.3.
Fig. 4 results show that increase potassium dihydrogen phosphate buffer solution concentration to 50mM, the symmetrical factor of main peak is 1.5, hangover
Improved.To protect chromatographic column, buffer salinity should not raise again.Therefore inventor's prioritizing selection pH=4.050mM phosphoric acid
A phase buffer solution of the potassium dihydrogen cushioning liquid as Li Gelieting content assaying methods.
1.4 need testing solution preparation methods determine
The volume ratio for selecting A phases and B phases is 72：Solvent of 28 mixed solution as Li Gelieting bulk drugs, inventor
Finding in an experiment, test sample concentration 0.2mg/mL, sample size is 10 microlitres, in gained chromatogram, Li Gelieting main peak
Peak height is about 600mAU, and Li Gelieting main peaks are indeformable, in linear response range in UV, and the purity factor is qualified.
Embodiment 2
In the present embodiment, inventor has investigated Li Gelieting in measure Li Gelieting bulk drugs determined by embodiment 1
The system suitability and the rate of recovery of the method for content, and describe in detail how under the chromatographic condition based on determined by embodiment 1
The chromatogram of acquisition, Li Gelieting content is calculated.
The preparation of 2.1 related solutions
Dilution (blank solution) is：A phases：B phase=72：28 mixed solution；
Standard control solution：Li Gelieting standard items about 20mg is taken, it is accurately weighed, put in 100mL volumetric flasks, use dilution
Make dissolving in right amount and be diluted to scale, shake up, produce standard control solution, it is parallel to prepare two parts, it is named as standard control solution 1
With standard control solution 2；
Need testing solution：Li Gelieting bulk drugs about 20mg is taken, it is accurately weighed, put in 100mL volumetric flasks, fitted with dilution
Amount makes dissolving and is diluted to scale, shakes up, and produces need testing solution, parallel to prepare two parts, is named as need testing solution 1 and for examination
Product solution 2.
2.2 chromatographic condition
Chromatographic column：5 microns of YMC-Pack ODS-AM 250*4.6mm；
Column temperature：35℃；
Detection wavelength：294nm；
Flow velocity：1.0mL/min；
Sampling volume：10 microlitres；
Run time：10min；
Mobile phase：A phases (50mM pH=4.0 potassium dihydrogen phosphate buffer solutions)：Potassium dihydrogen phosphate about 6.8g is taken, adds water 1L
Make dissolving, adjust pH=4.0 with phosphoric acid, shake up, filtered with 0.45 micron membrane filter, ultrasound degassing, produce；
B phases：Acetonitrile；
Isocratic elution：A phases：B phase=72：28.
2.3 associative operation
After baseline balance, blank solution is taken by 2.2 chromatographic condition sample introduction 1-2 pins (after system fully balances), Ran Houqu
Standard control solution 1 and 2 and need testing solution 1 and 2 press following sequence sample introduction, record chromatogram.Take and enter standard for the first time
2 pins of the standard control solution of (retinue) after preceding 3 pin and need testing solution of contrast solution 1, calculate the RSD of peak area, it is desirable to
≤ 2.0%；Such as enter repeatedly retinue control, calculated with method.It is required that RSD≤2.0%.
Wherein, sample introduction sequence is as shown in table 1,
Table 1：Sample introduction sequence
Wherein,
Blank solution testing result shows (chromatogram such as Fig. 5) that the detection method under 2.2 chromatographic conditions is interference-free；
Standard control solution collection of illustrative plates is as shown in Figure 6；
System suitability testing result is shown, utilizes the detection method under 2.2 chromatographic conditions, examination criteria contrast solution institute
Obtain in collection of illustrative plates, the symmetrical factor of main peak is between 0.8~2.0；The pin of 1 continuous sample introduction of standard control solution 5, main peak peak area RSD
System suitability no more than the detection method under 0.73%, 2.2 chromatographic condition is good.
Rate of recovery result shows, using the detection method under 2.2 chromatographic conditions, after the sample introduction of standard control solution 1 and 2,
The rate of recovery of detection method of the rate of recovery of standard reference material solution 2 under 99.0%~101.0%, 2.2 chromatographic condition is good.
Wherein, rate of recovery calculation formula is：
WS1：The sample weighting amount of Li Gelieting standard items, mg in standard control solution 1；
WS2：The sample weighting amount of Li Gelieting standard items, mg in standard control solution 2；
AS1：The average value of standard control solution 1 (continuous sample introduction 5 times) main peak peak area；
AS2：The average value of main peak peak area in standard control solution 2.
Need testing solution collection of illustrative plates is as shown in Figure 7.
The computational methods of the 2.4 Li Gelieting contents based on chromatogram
The content of Li Gelieting in need testing solution is calculated according to below equation：
Wherein：WS1For the sample weighting amount of Li Gelieting standard items in standard control solution 1, mg；
ATFor the average value of Li Gelieting main peaks peak area in need testing solution；
DTFor the extension rate of need testing solution；
AS1For standard control solution 1 (calculate take 2 pins of retinue control after the pin of repetition sample introduction 5 and need testing solution for the first time, after
Continuous calculating takes each 2 pin retinue control before and after need testing solution) in main peak peak area average value；
DS1For the extension rate of standard control solution 1；
WTFor the quality of Li Gelieting bulk drugs in need testing solution, mg；
P is the purity of Li Gelieting standard items；
W be Li Gelieting bulk drugs in moisture content, %.
In the description of this specification, reference term " one embodiment ", " some embodiments ", " example ", " specifically show
The description of example " or " some examples " etc. means specific features, structure, material or the spy for combining the embodiment or example description
Point is contained at least one embodiment or example of the present invention.In this manual, to the schematic representation of above-mentioned term not
Identical embodiment or example must be directed to.Moreover, specific features, structure, material or the feature of description can be with office
Combined in an appropriate manner in one or more embodiments or example.In addition, in the case of not conflicting, the skill of this area
Art personnel can be tied the different embodiments or example and the feature of different embodiments or example described in this specification
Close and combine.
Although embodiments of the invention have been shown and described above, it is to be understood that above-described embodiment is example
Property, it is impossible to limitation of the present invention is interpreted as, one of ordinary skill in the art within the scope of the invention can be to above-mentioned
Embodiment is changed, changed, replacing and modification.
Claims (8)
1. a kind of method of Li Gelieting contents in measure Li Gelieting bulk drugs, it is characterised in that
The Li Gelieting bulk drugs are analyzed by HPLC analytical method, to obtain chromatogram；And
Based on the chromatogram, the content of Li Gelieting in the Li Gelieting bulk drugs is determined,
Wherein, the high performance liquid chromatography uses following condition：
Chromatographic column is YMC-PACK ODS-AM, 4.6 × 250mm, 5 micron,
Detector is DAD,
Detection wavelength is 294nm,
Column temperature is 35 DEG C,
Mobile phase A is mutually 10~50mmol/L potassium phosphate buffer, the pH of the potassium phosphate buffer for 3.0~
5.0
Mobile phase B is mutually acetonitrile,
Flow velocity is 1.0mL/min,
Elute and use isocratic elution, the volume ratio of A phases and B phases is 72 in the isocratic elution:28,
Run time is 10min.
2. according to the method for claim 1, it is characterised in that the pH of the potassium phosphate buffer is 4.0.
3. according to the method for claim 1, it is characterised in that the mobile phase A is mutually 50mmol/L potassium dihydrogen phosphate
Buffer solution.
4. according to the method for claim 1, it is characterised in that the Li Gelieting bulk drugs are the shapes with need testing solution
What formula provided, wherein, the need testing solution is potassium dihydrogen phosphate-acetonitrile solution of Li Gelieting bulk drugs, and based on every
The milliliter need testing solution, the content of Li Gelieting bulk drugs is 0.2mg,
Wherein, the potassium dihydrogen phosphate-acetonitrile solution is the mixed solution of the A phases and B phases, the volume ratio of the A phases and B phases
For 72：28.
5. according to the method for claim 4, it is characterised in that the dosage of the need testing solution is 10 microlitres.
6. according to the method for claim 1, it is characterised in that the HPLC analytical method uses standard control
Solution, the standard control solution are potassium dihydrogen phosphate-acetonitrile solutions of Li Gelieting standard items, and based on described in every milliliter
Standard control solution, the quality of Li Gelieting standard items is 0.2mg.
7. according to the method for claim 1, it is characterised in that it is described to be based on the chromatogram, determine the Li Gelieting
Li Gelieting content is determined by below equation in bulk drug：
Wherein, WS1For the quality of Li Gelieting standard items in standard control solution；
ATFor Li Gelieting main peaks peak area in need testing solution；
DTFor the extension rate of need testing solution；
AS1For Li Gelieting main peak peak areas in standard control solution；
DS1For the extension rate of standard control solution；
WTFor the quality of Li Gelieting bulk drugs in need testing solution；
P is the purity of Li Gelieting standard items；
W is the content of moisture in Li Gelieting bulk drugs.
8. a kind of method of Li Gelieting contents in measure Li Gelieting bulk drugs, it is characterised in that
(1) chromatographic condition
Chromatographic column is YMC-PACK ODS-AM, 4.6 × 250mm, 5 micron,
Detector is DAD,
Detection wavelength is 294nm,
Column temperature is 35 DEG C,
Mobile phase A is mutually 50mmol/L potassium phosphate buffer, and the pH of the potassium phosphate buffer is 4.0,
Mobile phase B is mutually acetonitrile,
Flow velocity is 1.0mL/min,
Elute and use isocratic elution, the volume ratio of A phases and B phases is 72 in the isocratic elution:28,
Run time is 10min,
(2) blank solution is prepared
The volume ratio of A phases and B phases is 72：28 mixed solution as the blank solution,
(3) need testing solution is prepared
Accurately weighed Li Gelieting bulk drugs 20mg, puts in 100mL volumetric flasks, is dissolved with blank solution, and is ultrasonically treated, dilute
Release to scale, shake up, produce the need testing solution,
(4) standard control solution is prepared
Accurately weighed Li Gelieting standard items 20mg, puts in 100mL volumetric flasks, is dissolved with blank solution, and is ultrasonically treated, dilute
Release to scale, shake up, produce the standard control solution,
(5) by 10 microlitres of need testing solution injecting chromatographs, chromatogram is obtained, it is molten that test sample is calculated according to the chromatogram
Li Gelieting content in liquid,
Wherein, the content of Li Gelieting in test solution is calculated as follows, takes the average value of 2 measurement results as measure
As a result：
In formula, WS1For Li Gelieting standard items quality in standard control solution；
ATFor the average value of Li Gelieting main peaks peak area in need testing solution；
DTFor the extension rate of need testing solution；
AS1For the average value of Li Gelieting main peak peak areas in each 2 pin standard control solution before and after need testing solution；
DS1For the extension rate of standard control solution；
WTFor the quality of Li Gelieting bulk drugs in need testing solution；
P is the purity of Li Gelieting standard items；
W is the content of moisture in Li Gelieting bulk drugs；
The dosage of 1 pin standard control solution is 10 microlitres.
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| CN114235972A (en) * | 2021-10-28 | 2022-03-25 | 乳源东阳光药业有限公司 | Method for determining linagliptin impurity RBP-1 content |
| CN114235972B (en) * | 2021-10-28 | 2023-08-22 | 乳源东阳光药业有限公司 | Method for determining content of linagliptin impurity RBP-1 |
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Application publication date: 20180403 |