CN105527357A - Method for determining antioxidant BHT in insulin glargine injection - Google Patents
Method for determining antioxidant BHT in insulin glargine injection Download PDFInfo
- Publication number
- CN105527357A CN105527357A CN201610077845.XA CN201610077845A CN105527357A CN 105527357 A CN105527357 A CN 105527357A CN 201610077845 A CN201610077845 A CN 201610077845A CN 105527357 A CN105527357 A CN 105527357A
- Authority
- CN
- China
- Prior art keywords
- insulin glargine
- antioxidant bht
- bht
- glargine injecta
- mobile phase
- 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
- 108010057186 Insulin Glargine Proteins 0.000 title claims abstract description 42
- COCFEDIXXNGUNL-RFKWWTKHSA-N Insulin glargine Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)NCC(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 COCFEDIXXNGUNL-RFKWWTKHSA-N 0.000 title claims abstract description 42
- 229960002869 insulin glargine Drugs 0.000 title claims abstract description 42
- 239000003963 antioxidant agent Substances 0.000 title claims abstract description 40
- 230000003078 antioxidant effect Effects 0.000 title claims abstract description 40
- 238000000034 method Methods 0.000 title claims abstract description 24
- 238000002347 injection Methods 0.000 title abstract description 9
- 239000007924 injection Substances 0.000 title abstract description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 36
- 239000008363 phosphate buffer Substances 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000004128 high performance liquid chromatography Methods 0.000 claims abstract description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 16
- OOSZCNKVJAVHJI-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]piperazine Chemical compound C1=CC(F)=CC=C1CN1CCNCC1 OOSZCNKVJAVHJI-UHFFFAOYSA-N 0.000 claims description 8
- 239000011780 sodium chloride Substances 0.000 claims description 8
- 229940074545 sodium dihydrogen phosphate dihydrate Drugs 0.000 claims description 8
- 238000002203 pretreatment Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 4
- 239000000945 filler Substances 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 11
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 abstract description 10
- 238000001514 detection method Methods 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 7
- 238000009512 pharmaceutical packaging Methods 0.000 abstract 1
- 238000007781 pre-processing Methods 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 11
- 230000000052 comparative effect Effects 0.000 description 8
- 229940100630 metacresol Drugs 0.000 description 8
- 239000000243 solution Substances 0.000 description 7
- 238000011084 recovery Methods 0.000 description 6
- 239000002960 lipid emulsion Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000012452 mother liquor Substances 0.000 description 4
- 238000012856 packing Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000013112 stability test Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229920005549 butyl rubber Polymers 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- -1 BHT Chemical compound 0.000 description 1
- 244000043261 Hevea brasiliensis Species 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000006067 antibiotic powder Substances 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical class N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 1
- 239000004026 insulin derivative Substances 0.000 description 1
- 238000000622 liquid--liquid extraction Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 229920003052 natural elastomer Polymers 0.000 description 1
- 229920001194 natural rubber Polymers 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- CKRORYDHXIRZCH-UHFFFAOYSA-N phosphoric acid;dihydrate Chemical compound O.O.OP(O)(O)=O CKRORYDHXIRZCH-UHFFFAOYSA-N 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
Classifications
-
- 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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
Abstract
The invention discloses a method for determining antioxidant BHT in an insulin glargine injection and belongs to the field of drug packaging and drug compatibility. The method specifically adopts a HPLC (high performance liquid chromatography) method for detection, a mobile phase comprise acetonitrile, water and a phosphate buffer, a complex preprocessing means is avoided, a chromatographic peak of the antioxidant BHT is separated successfully from chromatographic peaks of insulin glargine and m-cresol according to the method, a trailing phenomenon is avoided, and the content of the antioxidant BHT in a sample is detected accurately.
Description
Technical field
The present invention relates to Key works Drug packing and drug compatibility field, particularly relate to a kind of method measuring antioxidant BHT in insulin glargine injecta.
Background technology
Drug packing material is to ensureing that the stability of medicine plays vital effect, closely bound up with the drug safety of people.The improper meeting of pharmaceutical packing material selection causes the migration of active constituents of medicine, absorption even chemical reaction occurs, and make drug failure, what have also can produce serious toxic and side effect.
Medicinal butyl rubber stopper, compared with natural rubber, due to good impermeability, stability, resistance to ag(e)ing and low precipitation, has become one of widely used material in medical packaging.Because the comparison of ingredients of plug is complicated, the kind of the compound comprised is also many, as directly touching pharmaceutical packing material, even if the chemical stability of butyl rubber plug is fine, compound wherein also likely can move in liquid, there is the possibility affecting drug effect or pollute medicine., there is the phenomenon that clarity exceeds standard in some antibiotic powder ampoule agent for injection, have bibliographical information may be relevant with plug used in storage process.
Antioxidant 2,6-di-tert-butyl-4-methy phenol, i.e. BHT, be one of known volatile composition be present in plug now, research shows that the liver taste of BHT to human body all have toxic action in various degree.BHT in research plug moves to the migration amount size in liquid, plays an important role to the Study on Compatibility of plug and medicine.Conventional art adopts the method for GC-MS for the detection major part of BHT migration amount, but the requirement of this method to instrument is higher, is difficult to popularize.
Insulin glargine injecta is insulin analog, clinically mainly be applicable to the diabetes needing insulinize, BHT in plug also exists the possibility moved in insulin glargine injecta equally, conventional art well can not detect the BHT in insulin glargine injecta, is therefore necessary to improve for this.
" pharmacy today " periodical describes the method using high performance liquid chromatography to detect BHT in fat emulsion injection in interim " high performance liquid chromatography detects the antioxidant BHT in fat emulsion injection " literary composition in 2015 05, the method has good Detection results to fat emulsion injection, but it needs before detecting to carry out complicated pretreatment process, when this method being applied in insulin glargine injecta, desirable result can not be obtained.Therefore be necessary to detect a kind of new detection method of exploitation for the BHT in insulin glargine injecta.
Summary of the invention
In view of this, the object of the invention is to overcome the deficiencies in the prior art, provide a kind of simple to operate and effectively can measure the method for antioxidant BHT in insulin glargine injecta.
In order to solve the problems of the technologies described above, the present invention adopts following scheme to realize:
Measure a method for antioxidant BHT in insulin glargine injecta, use high performance liquid chromatography to detect, and mobile phase is acetonitrile: water: phosphate buffer.
The method that " high performance liquid chromatography detects the antioxidant BHT in fat emulsion injection " in background technology is mentioned to is applied in insulin glargine injecta, can not do the trick, inventor is found by research, insulin glargine in insulin glargine injecta and bacteriostatic agent metacresol there will be chromatographic peak and trail under this chromatographic condition, thus affect the chromatographic peak of antioxidant BHT, based on this, inventor further finds, the pre-treatment means such as liquid-liquid extraction in prior art can be adopted insulin glargine and metacresol to be removed from sample, but this pre-treatment means are extremely complicated and efficiency is low, experimental error is large, organic reagent consumption is large, cost is higher.Inventor is by research and development, employ acetonitrile: water: phosphate buffer is used as mobile phase, antioxidant BHT chromatographic peak is separated with metacresol chromatographic peak with insulin glargine, thus lays the first stone for achieving antioxidant BHT in Accurate Measurement insulin glargine injecta.
Described phosphate buffer is for be dissolved in the water sodium dihydrogen phosphate dihydrate and sodium chloride, adjustment pH to 2.5 ~ 4 are prepared from, make in the mobile phase of final mixing, the concentration of sodium dihydrogen phosphate dihydrate is 0.0031 ~ 0.0052g/ml, and the concentration of sodium chloride is 0 ~ 0.0032g/ml.By further optimizing the consumption of sodium dihydrogen phosphate dihydrate and sodium chloride, avoid the precipitation of salt, sodium dihydrogen phosphate dihydrate ensure that the pH of mobile phase, and insulin glargine and metacresol can be made to go out peak in advance, avoids the chromatographic peak affecting test substance antioxidant BHT; Sodium chloride can modify the peak type of BHT, and the parameter at peak is more easily read.
Further, between mobile phase composition, volume ratio is acetonitrile: water: phosphate buffer=65 ~ 75:10:15 ~ 25.By the optimization to three's proportioning, under the prerequisite being successfully separated three peaks, avoid and separate out salt and cause the damage of instrument.
Further, high performance liquid chromatography also comprises following condition:
Chromatographic column: C18 filler chromatographic column;
Column temperature: 30 ~ 40 DEG C;
Flow velocity: 1 ~ 1.5ml/min.
Before sample introduction, insulin glargine injecta sample needs to carry out pre-treatment, is specially and uses methyl alcohol or acetonitrile to mix with insulin glargine injecta.First sample is diluted, the solubleness of antioxidant BHT in insulin glargine injecta can be increased, and dilute the concentration of insulin glargine and metacresol.
Compared with prior art, the present invention has following beneficial effect:
1, pre-treatment of the present invention is simple, and only need with methyl alcohol or dilution in acetonitrile sample, the used time is few, and organic reagent consumption is few, high-efficiency environment friendly, and reduce operate miss, test findings accurately and reliably;
2, the present invention can avoid insulin glargine, the metacresol even existence of its structure similar substance on the impact of antioxidant BHT chromatographic peak, thus accurately detects the content of antioxidant BHT.
Accompanying drawing explanation
Fig. 1 is insulin glargine injecta mark-on chromatogram in embodiment 1;
Fig. 2 is the typical curve of antioxidant BHT in embodiment 1;
Fig. 3 is comparative example 1 sample mark-on chromatogram;
Fig. 4 is comparative example 2 sample mark-on chromatogram;
Fig. 5 is comparative example 3 sample mark-on chromatogram;
Fig. 6 is comparative example 4 sample mark-on chromatogram.
Embodiment
In order to allow those skilled in the art understand technical scheme of the present invention better, below in conjunction with accompanying drawing, the present invention is further elaborated.
Embodiment 1
Detected object: antioxidant BHT;
Detect matrix: insulin glargine injecta, for being administered to Types of Medicine solution;
Detection method: high performance liquid chromatography, C18 filler chromatographic column, UV-detector, mobile phase is acetonitrile: water: phosphate buffer, and three's volume ratio is 65:10:25, column temperature 35 DEG C, flow velocity 1ml/min, determined wavelength 280nm;
Being formulated as follows of described phosphate buffer: get sodium dihydrogen phosphate dihydrate 20.7g, the 800ml that adds water dissolves, and with phosphorus acid for adjusting pH to 2.5, adds sodium chloride 12.8g, adds water to 1000ml.
1. specificity test
Get the BHT standard mother liquor that 5ml insulin glargine injecta adds 1ml, by methanol constant volume to 10ml, enter high performance liquid chromatograph 20 μ l according to above-mentioned chromatographic condition.As shown in Figure 1, the retention time of antioxidant BHT is 23.1min.
2. linear test
Antioxidant BHT is contrasted storing solution and be diluted to 0.4364,1.091,2.182,5.455,10.91,21.82 μ g/ml, sample introduction 20 μ l, carries out HPLC mensuration respectively.Each concentration surveys 3 times, averages.As shown in Figure 2, linear equation is C=4.846 × 10
-5a-8.603 × 10
-2, R
2=0.9996, show that antioxidant BHT is good in 0.4364 ~ 21.82 μ g/ml internal linear.
3. precision test
Get the antioxidant BHT contrast storing solution that concentration is 0.4364 μ g/ml, 2.182 μ g/ml, 10.91 μ g/ml, injection liquid chromatography, sample introduction 20 μ l.Continuous sample introduction 3 pin, record chromatographic peak, relative standard's difference (RSD) of peak area is as following table:
Table 1 Precision test result
4. stability test
Get each 20 μ l of antioxidant BHT contrast storing solution that concentration is 0.2182 μ g/ml, 1.091 μ g/ml, 5.455 μ g/ml, high performance liquid chromatography is injected respectively at 0h and 24h, record chromatogram, the relative standard deviation value (RSD) of peak area sees the following form.
Table 2 stability test result
5. lowest detectable limit and minimum quantitative limit
BHT being contrasted storing solution, to be constantly diluted to signal to noise ratio (S/N ratio) be 3, and obtain instrument and detect and be limited to 0.1 μ g/ml, sample detection limit is 0.21 μ g/ml.BHT being contrasted storing solution, to be constantly diluted to signal to noise ratio (S/N ratio) be 10, and obtain instrument quantitative and be limited to 0.3 μ g/ml, sample amounts is limited to 0.6 μ g/ml.
6. recovery test in insulin glargine injecta
Get the BHT standard mother liquor that 5ml insulin glargine injecta adds 50 μ l, 0.25ml, 1ml, by methanol constant volume to 10ml.With injection liquid chromatography after 0.45 μm of membrane filtration, sample introduction 20 μ l, record chromatogram, calculates the recovery.
Table 3 recovery test result
To sum up, insulin glargine injecta is after dilution, and the method accurately can detect antioxidant BHT.
Embodiment 2
Except column temperature is 40 DEG C, flow velocity is 1.5ml/min, acetonitrile: water: phosphate buffer=75:10:15, and phosphate buffer is adopt outside the sodium dihydrogen phosphate dihydrate of 12.4g and the preparation of 0g sodium chloride, and other condition is with embodiment 1.
After tested, during linear test, BHT is good in 0.4364 ~ 21.82 μ g/ml internal linear, R
2=0.9997; During precision test, RSD is between 0.21 ~ 0.76%; During stability test, RSD is between 0.59 ~ 1.54%; In insulin glargine injecta in recovery test, average recovery rate is between 98.12 ~ 109.31%, and RSD is between 0.13 ~ 0.54%.To sum up, the method accurately can detect antioxidant BHT.
Comparative example 1
During except preparation mobile phase, regulate pH to 2.0, get outside the antioxidant BHT contrast storing solution sample introduction of 2.535 μ g/ml, other chromatographic condition is with embodiment 1, and as shown in Figure 3, under the mobile phase condition of pH=2, before antioxidant BHT goes out peak, baseline rises obviously.
Comparative example 2
Except mobile phase is methyl alcohol: water=80:20, getting insulin glargine injecta, to add antioxidant BHT standard mother liquor to the concentration of antioxidant BHT be 2.7275 μ g/ml, outside sample introduction 20 μ l, other chromatographic condition is with embodiment 1, as shown in Figure 4, under the condition of this mobile phase, the recovery rate variance of antioxidant BHT, does not go out peak substantially.
Comparative example 3
Except mobile phase is acetonitrile: water: phosphate buffer=63:12:25, getting insulin glargine injecta, to add antioxidant BHT standard mother liquor to the concentration of antioxidant BHT be 2.7275 μ g/ml, outside sample introduction 20 μ l, other chromatographic condition is with embodiment 1, as shown in Figure 5, proportioning between the component changing mobile phase, antioxidant BHT does not go out peak in 50min, and detection time is long.
Comparative example 4
During except preparation phosphate buffer, dihydrogen phosphate dihydrate is outside 11g, and other chromatographic condition is with embodiment 1.As shown in Figure 6, although can successfully BHT chromatographic peak be separated with metacresol with insulin glargine, metacresol and insulin glargine peak shape poor, BHT peak type is asymmetric.
Claims (5)
1. measure a method for antioxidant BHT in insulin glargine injecta, it is characterized in that, use high performance liquid chromatography to detect, and mobile phase is acetonitrile: water: phosphate buffer.
2. the method for antioxidant BHT in mensuration insulin glargine injecta according to claim 1, it is characterized in that, described phosphate buffer is for be dissolved in the water sodium dihydrogen phosphate dihydrate and sodium chloride, adjustment pH to 2.5 ~ 4 are prepared from, make in the mobile phase of final mixing, the concentration of sodium dihydrogen phosphate dihydrate is 0.0031 ~ 0.0052g/ml, and the concentration of sodium chloride is 0 ~ 0.0032g/ml.
3. the method for antioxidant BHT in mensuration insulin glargine injecta according to claim 2, it is characterized in that, between mobile phase composition, volume ratio is acetonitrile: water: phosphate buffer=65 ~ 75:10:15 ~ 25.
4. the method for antioxidant BHT in mensuration insulin glargine injecta according to claim 1, it is characterized in that, high performance liquid chromatography also comprises following condition:
Chromatographic column: C18 filler chromatographic column;
Column temperature: 30 ~ 40 DEG C;
Flow velocity: 1 ~ 1.5ml/min.
5. the method for antioxidant BHT in mensuration insulin glargine injecta according to claim 1, it is characterized in that, insulin glargine injecta sample needs to carry out pre-treatment, is specially and uses methyl alcohol or acetonitrile to mix with insulin glargine injecta.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610077845.XA CN105527357B (en) | 2016-02-04 | 2016-02-04 | A kind of method of antioxidant BHT in measure insulin glargine injecta |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610077845.XA CN105527357B (en) | 2016-02-04 | 2016-02-04 | A kind of method of antioxidant BHT in measure insulin glargine injecta |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105527357A true CN105527357A (en) | 2016-04-27 |
| CN105527357B CN105527357B (en) | 2018-02-27 |
Family
ID=55769711
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610077845.XA Expired - Fee Related CN105527357B (en) | 2016-02-04 | 2016-02-04 | A kind of method of antioxidant BHT in measure insulin glargine injecta |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105527357B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112067737A (en) * | 2020-09-27 | 2020-12-11 | 江苏知原药业有限公司 | Method for detecting antioxidant in minoxidil foaming agent |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080248099A1 (en) * | 2005-11-11 | 2008-10-09 | Ishii Douglas N | Method for Treating Disease or Disorder of Adult Central Nervous System Associated with Tissue Shrinkage or Atrophy by Administration of Insulin |
| CN102928545A (en) * | 2012-11-09 | 2013-02-13 | 江苏吉贝尔药业有限公司 | Method for measuring BHT (butylated hydroxytoluene) content in Pranoprofen eye drops |
| CN104374843A (en) * | 2014-11-11 | 2015-02-25 | 广东东阳光药业有限公司 | Method for simultaneously detecting methylparaben, propylparaben and dibutyl hydroxy toluene in gel |
| CN104688678A (en) * | 2015-02-05 | 2015-06-10 | 通化东宝药业股份有限公司 | Preparation method of insulin glargine injection and insulin glargine injection prepared by using preparation method |
-
2016
- 2016-02-04 CN CN201610077845.XA patent/CN105527357B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080248099A1 (en) * | 2005-11-11 | 2008-10-09 | Ishii Douglas N | Method for Treating Disease or Disorder of Adult Central Nervous System Associated with Tissue Shrinkage or Atrophy by Administration of Insulin |
| CN102928545A (en) * | 2012-11-09 | 2013-02-13 | 江苏吉贝尔药业有限公司 | Method for measuring BHT (butylated hydroxytoluene) content in Pranoprofen eye drops |
| CN104374843A (en) * | 2014-11-11 | 2015-02-25 | 广东东阳光药业有限公司 | Method for simultaneously detecting methylparaben, propylparaben and dibutyl hydroxy toluene in gel |
| CN104688678A (en) * | 2015-02-05 | 2015-06-10 | 通化东宝药业股份有限公司 | Preparation method of insulin glargine injection and insulin glargine injection prepared by using preparation method |
Non-Patent Citations (4)
| Title |
|---|
| BAHRUDDIN SAAD 等: "Determination of synthetic phenolic antioxidants in food items using reversed-phase HPLC", 《FOOD CHEMISTRY》 * |
| LI XIU-QIN 等: "Analysis of synthetic antioxidants and preservatives in edible vegetable oil by HPLC/TOF-MS", 《FOOD CHEMISTRY》 * |
| 蔡玉枝 等: "高效液相色谱法快速测定食品中抗氧化剂BHA、BHT", 《分析测试学报》 * |
| 赵榕 等: "月饼中常用抗氧化剂、防腐剂和甜味剂同时测定的方法研究", 《中国卫生检验杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112067737A (en) * | 2020-09-27 | 2020-12-11 | 江苏知原药业有限公司 | Method for detecting antioxidant in minoxidil foaming agent |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105527357B (en) | 2018-02-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Christophidis et al. | Comparison of liquid-and gas-liquid chromatographic assays of 5-fluorouracil in plasma. | |
| CN109966244A (en) | A kind of pharmaceutical composition containing Le Temowei | |
| Consortti et al. | A critical review of analytical methods for quantification of Cefotaxime | |
| CN103099790B (en) | A kind of tablet containing everolimus and preparation method thereof | |
| de Oliveira Rossini et al. | A simple and precise conductometric method for the determination of losartan in pharmaceutical products | |
| Yang et al. | The simultaneous separation and determination of six flavonoids and troxerutin in rat urine and chicken plasma by reversed-phase high-performance liquid chromatography with ultraviolet–visible detection | |
| CN111948299B (en) | Method for determining content of disodium edetate in posaconazole injection | |
| CN105388225A (en) | Analysis and detection method for UDPC in medicinal preparation containing citicoline sodium | |
| CN105527357A (en) | Method for determining antioxidant BHT in insulin glargine injection | |
| Agarwal | Chromatographic estimation of iothalamate and p-aminohippuric acid to measure glomerular filtration rate and effective renal plasma flow in humans | |
| Wahab et al. | Development of RP-HPLC method for the simultaneous determination of mefenamic acid and drotaverine HCl combined tablet dosage form | |
| Chulavatnatol et al. | High-performance liquid chromatographic determination of amoxicillin in urine using solid-phase, ion-pair extraction and ultraviolet detection | |
| CN103463614A (en) | Argatroban injection and preparation method thereof | |
| Chaudhary et al. | Validated reverse phase HPLC method for the determination of DEHP content in reconstituting diluents and in reconstituted solutions of imipenem and cilastatin for injection | |
| CN102759586B (en) | Method for measuring content of sulfhydryl compound in composition by high performance liquid chromatography | |
| CN105181859A (en) | Cysteine hydrochloride in acetaminophen injection and test method of degradation product cystine | |
| Pujari et al. | Determination of hydroxyurea in plasma and peritoneal fluid by high-performance liquid chromatography using electrochemical detection | |
| Wilson et al. | Stability of milrinone and epinephrine, atropine sulfate, lidocaine hydrochloride, or morphine sulfate injection | |
| Shea et al. | High-performance liquid chromatographic measurement of exogenous thiosulfate in urine and plasma | |
| CN103860461A (en) | Medicinal composition containing active component ambroxol hydrochloride | |
| CN108152432B (en) | High performance liquid detection method for lotafloxacin tablets | |
| CN102590385B (en) | Method for detecting picoplatin and impurities thereof | |
| CN112730703A (en) | Method for detecting substances related to ganirelix acetate injection | |
| Sultan et al. | Stability Assessment of Cephradine Suspension Formulated in Bangladesh | |
| CN102928525A (en) | Method for detecting related substance II of cefpirome in cefpirome sulfate/sodium chloride injection |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20180227 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |