CN105606746A - HPLC (high-performance liquid chromatography) detection method for octylated diphenylamine in lansoprazole - Google Patents
HPLC (high-performance liquid chromatography) detection method for octylated diphenylamine in lansoprazole Download PDFInfo
- Publication number
- CN105606746A CN105606746A CN201510981513.XA CN201510981513A CN105606746A CN 105606746 A CN105606746 A CN 105606746A CN 201510981513 A CN201510981513 A CN 201510981513A CN 105606746 A CN105606746 A CN 105606746A
- Authority
- CN
- China
- Prior art keywords
- water
- lansoprazole
- octylated diphenylamine
- detection method
- reference substance
- 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
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical compound C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 title claims abstract description 182
- 229960003174 lansoprazole Drugs 0.000 title claims abstract description 62
- 238000001514 detection method Methods 0.000 title claims abstract description 28
- 238000004128 high performance liquid chromatography Methods 0.000 title claims abstract description 21
- MJIHNNLFOKEZEW-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1 MJIHNNLFOKEZEW-UHFFFAOYSA-N 0.000 title claims abstract 9
- 238000012360 testing method Methods 0.000 claims abstract description 80
- 239000013558 reference substance Substances 0.000 claims description 51
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 claims description 33
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 claims description 21
- 239000007788 liquid Substances 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- 238000012856 packing Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 abstract description 11
- 238000002347 injection Methods 0.000 abstract description 11
- 238000011084 recovery Methods 0.000 abstract description 7
- 239000000243 solution Substances 0.000 description 65
- SIXIIKVOZAGHPV-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=C[CH]C2=N1 SIXIIKVOZAGHPV-UHFFFAOYSA-N 0.000 description 53
- 239000000945 filler Substances 0.000 description 40
- 238000000034 method Methods 0.000 description 29
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- 230000014759 maintenance of location Effects 0.000 description 23
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 14
- 239000000377 silicon dioxide Substances 0.000 description 14
- 239000002245 particle Substances 0.000 description 13
- 238000004811 liquid chromatography Methods 0.000 description 10
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 238000012216 screening Methods 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 6
- 238000010812 external standard method Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000012490 blank solution Substances 0.000 description 3
- 239000002075 main ingredient Substances 0.000 description 3
- 229920005557 bromobutyl Polymers 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000027119 gastric acid secretion Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 239000005022 packaging material Substances 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 240000005373 Panax quinquefolius Species 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000001711 oxyntic cell Anatomy 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
-
- 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
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses an HPLC (high-performance liquid chromatography) detection method for octylated diphenylamine in lansoprazole. A test proves that octylated diphenylamine in lansoprazole can be separated and detected, a detection result is accurate and reliable, and the detection method has the advantages of excellent linear relationship, high precision, good stability, good repeatability, high recovery rate, simplicity and convenience in operation, low cost and the like, can effectively monitor the quality of lansoprazole for injection and is suitable for popularization and application.
Description
Technical field
The present invention relates to the HPLC detection method of octylated diphenylamine in Lansoprazole.
Background technology
Lansoprazole (Lansoprazole, 2-[[[3-methyl-4-(2,2,2-trifluoro ethoxy)-2-pyridine radicals] methyl]-sulfinyl]-1H-benzimidazole, molecular formula: C16H14F3N3O2S; molecular weight: 369.37) be a kind of Proton pump inhibitor thing; it can selectively suppress the ATP enzyme of parietal cell; it is the anti-ulcer medicament of gastric acid secretion inhibiting; it can suppress helicobacter pylori; protection and promotion stomach lining ulcer healing, the gastric acid secretion that a variety of causes is caused is crossed Sheng and is all had good effect.
Lansoprazole for injecting (LansoprazoleforInjection) is one of the most common Lansoprazole product. It adopts control glass injection and brominated butyl rubber plug as packaging material conventionally. But, packaging material with the contact process of main ingredient in, some special component (for example: sulphur, phenol, octylated diphenylamine etc.) can infiltrate in main ingredient under certain conditions, affects the security of the clinical use of main ingredient.
Octylated diphenylamine is one of composition of brominated butyl rubber plug, and has certain toxicity. Therefore, measure the content of impurity octylated diphenylamine in Lansoprazole for injecting product, have great significance for the quality control of Lansoprazole for injecting. But the relevant report of having not yet to see.
Summary of the invention
For addressing the above problem, the invention provides the HPLC detection method of octylated diphenylamine in a kind of Lansoprazole, it comprises the following steps:
A, prepare need testing solution:
Get Lansoprazole sample to be measured, mobile phase dissolves, and prepares need testing solution;
B, prepare the reference substance solution of octylated diphenylamine:
Get octylated diphenylamine reference substance, mobile phase dissolves, and prepares the reference substance solution of octylated diphenylamine;
C, respectively need testing solution and reference substance solution are injected to high performance liquid chromatograph and detect, chromatographic condition is as follows:
Chromatographic column: C18 chromatographic column; Be its fixing be filler with octadecylsilane chemically bonded silica mutually;
Mobile phase: methanol-water or acetonitrile-water;
Detect wavelength: 210 ± 5nm, preferably detecting wavelength is 210 ± 2nm;
D, calculate the octylated diphenylamine content in Lansoprazole according to testing result.
Further, in step c, the specification of described chromatographic column is: internal diameter 4.6mm, length 50mm, packing material size 5 μ m.
Further, in step c, the model of described chromatographic column is WatersXbridgeshieldRP18.
Further, in step c, the volume ratio of described methanol-water is 20%:80%～30%:70%; The volume ratio of acetonitrile-water is 20%:80%～30%:70%.
Further, in step c, the mixed solvent that described mobile phase is following volume ratio:
Methanol-water=20:80, methanol-water=25:75, methanol-water=30:70, acetonitrile-water=20:80, acetonitrile-water=25:75 or acetonitrile-water=30:70.
Further, in step a, the concentration of need testing solution is 0.4～0.6mg/mL; In step b, the concentration of reference substance solution is 0.1～1.0 μ g/mL.
Further, in step c, the column temperature of described chromatographic condition is 35 DEG C～45 DEG C, and preferred column temperature is 35 DEG C～40 DEG C; Flow velocity is 0.8mL/min～1.2mL/min, and preferred flow velocity is 0.8mL/min～1.0mL/min.
Further, in step c, the volume ratio of described methanol-water is 20%:80%～25%:75%; The volume ratio of acetonitrile-water is 20%:80%～25%:75%.
Further, in step c, the sample size of described chromatographic condition is 20 μ L.
Further, described Lansoprazole sample is Lansoprazole for injecting.
Verify through methodology, the HPLC detection method of octylated diphenylamine in Lansoprazole of the present invention, octylated diphenylamine in Lansoprazole is separated and detected, testing result accurately, reliably, and there is the plurality of advantages such as linear relationship excellence, precision are high, good stability, reproducible, the rate of recovery good, easy and simple to handle, cost is low, quality that can effective monitoring Lansoprazole for injecting, is suitable for applying
Obviously,, according to foregoing of the present invention, according to ordinary skill knowledge and the customary means of this area, not departing under the above-mentioned basic fundamental thought of the present invention prerequisite, can also make amendment, replacement or the change of other various ways.
The detailed description of the invention of form by the following examples, is described in further detail foregoing of the present invention again. But this should be interpreted as to the scope of the above-mentioned theme of the present invention only limits to following example. All technology realizing based on foregoing of the present invention all belong to scope of the present invention.
Brief description of the drawings
Fig. 1 is the testing result of the inventive method to solvent interference test in embodiment 1.
Fig. 2 is the canonical plotting of embodiment 11.
Fig. 3-5 are the testing result of embodiment 11 specificity tests: Fig. 3 is (a) need testing solution; Fig. 4 is (b) reference substance solution; Fig. 5 is (c) solvent blank solution.
Detailed description of the invention
The raw material, the equipment that in the specific embodiment of the invention, use are known product, obtain by buying commercially available prod.
High performance liquid chromatograph (model: LC-2010CHT, manufacturer: Japanese Shimadzu company).
Electronic balance (model: AUW220D, manufacturer: Japanese Shimadzu company).
Injection rope draw azoles (lot number: 130701, specification: 30mg, source: Chengdu Bai Yujin Ge Lai pharmaceutcal corporation, Ltd).
Octylated diphenylamine (lot number: 20130301, source: in Shanghai AoKe Industrial Co., Ltd.).
Embodiment 1
1, detect determining of wavelength
It is appropriate that precision takes Lansoprazole, is mixed with the solution that concentration is 20 μ g/mL with mobile phase (methanol-water=25:75), as need testing solution.
It is appropriate that precision takes reference substance (octylated diphenylamine), is mixed with the solution that concentration is 20 μ g/mL, in contrast product solution with mobile phase (methanol-water=25:75).
Get above-mentioned need testing solution, reference substance solution, in 200nm～400nm wave-length coverage, scan, result of the test is in table 1.
Table 1, UV scanning result of the present invention
| Project | Spike long (nm) | Peak value | Paddy wavelength (nm) | Valley |
| Need testing solution | 211 | 0.721 | 240 | 0.001 |
| Reference substance solution | 210 | 0.865 | 272 | 0.005 |
Result of the test shows, detects wavelength within the scope of 205nm～215nm, is all applicable to high-efficiency liquid chromatography method for detecting of the present invention; Preferred detection wavelength is 210 ± 2nm.
2, system suitability and solvent interference test
Prepare need testing solution: take Lansoprazole for injecting 25mg, be placed in 50mL measuring bottle, add mobile phase appropriate, jolting 10 minutes, adds mobile phase and be diluted to scale, shakes up, as need testing solution.
Preparation reference substance solution: take octylated diphenylamine reference substance 5mg, be placed in 100mL measuring bottle, precision measures 1mL, is placed in 100mL measuring bottle, adds mobile phase and is diluted to scale, shakes up, in contrast product solution.
Adopt RPLC to detect:
The filler of chromatographic column: with octadecylsilane chemically bonded silica be filler;
The model of chromatographic column is WatersXbridgeshieldRP18, and specification is: internal diameter is 4.6mm, and length is 50mm, and filler particle diameter is 5 μ m;
Mobile phase: methanol-water (volume ratio is 25:75);
Column temperature: 40 DEG C;
Flow velocity: 1.0mL/min;
Detect wavelength: 210nm;
Sample size: 20 μ L.
Solvent interference test: measure 20 μ L mobile phase solution injection liquid chromatographies, record chromatogram, in blank solvent chromatogram with octylated diphenylamine corresponding position, occur without chromatographic peak.
The testing result of system suitability is shown in Fig. 1, separating degree between Lansoprazole (retention time is 0.575min) and octylated diphenylamine reference substance (retention time is 25.935min) is 21.123, theoretical cam curve (calculating by octylated diphenylamine chromatographic peak) is 49315, and tailing factor is 0.999.
The above results proves, HPLC detection method of the present invention can accurately detect the content of octylated diphenylamine in Lansoprazole for injecting.
3, high-efficiency liquid chromatography method for detecting
Prepare need testing solution: take Lansoprazole for injecting 25mg, be placed in 50mL measuring bottle, add mobile phase (methanol-water=25:75) appropriate, jolting 10 minutes, adds mobile phase and be diluted to scale, shakes up, as need testing solution.
Preparation reference substance solution: take octylated diphenylamine reference substance 5mg, be placed in 100mL measuring bottle, precision measures 1mL, is placed in 100mL measuring bottle, adds mobile phase (methanol-water=25:75) and is diluted to scale, shakes up, in contrast product solution.
Respectively need testing solution and reference substance solution are injected to high performance liquid chromatograph detection, adopt RPLC to detect, chromatographic condition is as follows:
The filler of chromatographic column: with octadecylsilane chemically bonded silica be filler;
The model of chromatographic column is WatersXbridgeshieldRP18, and specification is: internal diameter is 4.6mm, and length is 50mm, and filler particle diameter is 5 μ m;
Mobile phase: methanol-water (volume ratio is 25:75);
Column temperature: 40 DEG C;
Flow velocity: 1.0mL/min;
Detect wavelength: 210nm;
Sample size: 20 μ L.
Calculate the content of octylated diphenylamine in Lansoprazole for injecting according to external standard method, in test sample, do not detect octylated diphenylamine.
Embodiment 2
The filler of chromatographic column: with octadecylsilane chemically bonded silica be filler;
The model of chromatographic column is WatersXbridgeshieldRP18, and specification is: internal diameter is 4.6mm, and length is 50mm, and filler particle diameter is 5 μ m;
Mobile phase: methanol-water (volume ratio is 25:75);
Column temperature: 40 DEG C;
Flow velocity: 1.0mL/min;
Detect wavelength: 210nm;
Sample size: 20 μ L.
Carry out interference test according to the method for embodiment 1, result shows: the separating degree between Lansoprazole (retention time is 0.575min) and octylated diphenylamine reference substance (retention time is 25.935min) is 21.123, theoretical cam curve (calculating by octylated diphenylamine chromatographic peak) is 49315, and tailing factor is 0.999.
Visible, this chromatographic condition can accurately detect the content of octylated diphenylamine in Lansoprazole for injecting.
Embodiment 3
Adopt RPLC to detect:
The filler of chromatographic column: with octadecylsilane chemically bonded silica be filler;
The model of chromatographic column is WatersXbridgeshieldRP18, and specification is: internal diameter is 4.6mm, and length is 50mm, and filler particle diameter is 5 μ m;
Mobile phase: methanol-water (volume ratio is 20:80);
Column temperature: 40 DEG C;
Flow velocity: 1.0mL/min;
Detect wavelength: 210nm;
Sample size: 20 μ L.
Carry out system suitability according to the method for embodiment 1, result shows: the separating degree between Lansoprazole (retention time is 1.207min) and octylated diphenylamine reference substance (retention time is 29.965min) is 25.723, theoretical cam curve (calculating by octylated diphenylamine chromatographic peak) is 41278, and tailing factor is 0.992.
Visible, this chromatographic condition can accurately detect the content of octylated diphenylamine in Lansoprazole for injecting.
Embodiment 4
Adopt RPLC to detect:
The filler of chromatographic column: with octadecylsilane chemically bonded silica be filler;
The model of chromatographic column is WatersXbridgeshieldRP18, and specification is: internal diameter is 4.6mm, and length is 50mm, and filler particle diameter is 5 μ m;
Mobile phase: methanol-water (volume ratio is 30:70);
Column temperature: 40 DEG C;
Flow velocity: 1.0mL/min;
Detect wavelength: 210nm;
Sample size: 20 μ L.
Carry out system suitability according to the method for embodiment 1, result shows: the separating degree between Lansoprazole (retention time is 0.551min) and octylated diphenylamine reference substance (retention time is 22.771min) is 18.756, theoretical cam curve (calculating by octylated diphenylamine chromatographic peak) is 78812, and tailing factor is 0.987.
Visible, this chromatographic condition can accurately detect the content of octylated diphenylamine in Lansoprazole for injecting.
Embodiment 5
Adopt RPLC to detect:
The filler of chromatographic column: with octadecylsilane chemically bonded silica be filler;
The model of chromatographic column is WatersXbridgeshieldRP18, and specification is: internal diameter is 4.6mm, and length is 50mm, and filler particle diameter is 5 μ m;
Mobile phase: acetonitrile-water (volume ratio is 20:80);
Column temperature: 40 DEG C;
Flow velocity: 1.0mL/min;
Detect wavelength: 210nm;
Sample size: 20 μ L.
Carry out system suitability according to the method for embodiment 1, result shows: the separating degree between Lansoprazole (retention time is 0.802min) and octylated diphenylamine reference substance (retention time is 26.759min) is 22.828, theoretical cam curve (calculating by octylated diphenylamine chromatographic peak) is 75123, and tailing factor is 0.976.
Visible, this chromatographic condition can accurately detect the content of octylated diphenylamine in Lansoprazole for injecting.
Embodiment 6
Adopt RPLC to detect:
The filler of chromatographic column: with octadecylsilane chemically bonded silica be filler;
The model of chromatographic column is WatersXbridgeshieldRP18, and specification is: internal diameter is 4.6mm, and length is 50mm, and filler particle diameter is 5 μ m;
Mobile phase: acetonitrile-water (volume ratio is 25:75);
Column temperature: 40 DEG C;
Flow velocity: 1.0mL/min;
Detect wavelength: 210nm;
Sample size: 20 μ L.
Carry out system suitability according to the method for embodiment 1, result shows: the separating degree between Lansoprazole (retention time is 0.857min) and octylated diphenylamine reference substance (retention time is 28.223min) is 25.022, theoretical cam curve (calculating by octylated diphenylamine chromatographic peak) is 67725, and tailing factor is 0.961.
Visible, this chromatographic condition can accurately detect the content of octylated diphenylamine in Lansoprazole for injecting.
Embodiment 7
Adopt RPLC to detect:
The filler of chromatographic column: with octadecylsilane chemically bonded silica be filler;
The model of chromatographic column is WatersXbridgeshieldRP18, and specification is: internal diameter is 4.6mm, and length is 50mm, and filler particle diameter is 5 μ m;
Mobile phase: acetonitrile-water (volume ratio is 30:70);
Column temperature: 40 DEG C;
Flow velocity: 1.0mL/min;
Detect wavelength: 210nm;
Sample size: 20 μ L.
Carry out system suitability according to the method for embodiment 1, result shows: the separating degree between Lansoprazole (retention time is 0.428min) and octylated diphenylamine reference substance (retention time is 19.712min) is 15.157, theoretical cam curve (calculating by octylated diphenylamine chromatographic peak) is 99877, and tailing factor is 1.002.
Visible, HPLC detection method of the present invention can accurately detect the content of octylated diphenylamine in Lansoprazole for injecting.
Embodiment 8
Adopt RPLC to detect:
The filler of chromatographic column: with octadecylsilane chemically bonded silica be filler;
The model of chromatographic column is WatersXbridgeshieldRP18, and specification is: internal diameter is 4.6mm, and length is 50mm, and filler particle diameter is 5 μ m;
Mobile phase: methanol-water (volume ratio is 25:75);
Column temperature: 35 DEG C;
Flow velocity: 0.8mL/min;
Detect wavelength: 210nm;
Sample size: 20 μ L.
Carry out system suitability according to the method for embodiment 1, result shows: the separating degree between Lansoprazole (retention time is 0.828min) and octylated diphenylamine reference substance (retention time is 29.077min) is 25.167, theoretical cam curve (calculating by octylated diphenylamine chromatographic peak) is 87895, and tailing factor is 1.031.
Visible, this chromatographic condition can accurately detect the content of octylated diphenylamine in Lansoprazole for injecting.
Embodiment 9
Adopt RPLC to detect:
The filler of chromatographic column: with octadecylsilane chemically bonded silica be filler;
The model of chromatographic column is WatersXbridgeshieldRP18, and specification is: internal diameter is 4.6mm, and length is 50mm, and filler particle diameter is 5 μ m;
Mobile phase: methanol-water (volume ratio is 25:75);
Column temperature: 45 DEG C;
Flow velocity: 1.2mL/min;
Detect wavelength: 210nm;
Sample size: 20 μ L.
Carry out system suitability according to the method for embodiment 1, result shows: the separating degree between Lansoprazole (retention time is 0.438min) and octylated diphenylamine reference substance (retention time is 20.221min) is 17.981, theoretical cam curve (calculating by octylated diphenylamine chromatographic peak) is 10117, and tailing factor is 1.025.
Visible, this chromatographic condition can accurately detect the content of octylated diphenylamine in Lansoprazole for injecting.
Embodiment 10 chromatographic condition screening of the present invention
1, mobile phase screening test
Select different mobile phases to carry out screening test, other chromatographic conditions are as follows:
The filler of chromatographic column: with octadecylsilane chemically bonded silica be filler;
The model of chromatographic column is WatersXbridgeshieldRP18, and specification is: internal diameter is 4.6mm, and length is 50mm, and filler particle diameter is 5 μ m;
Mobile phase: table 2;
Column temperature: 40 DEG C;
Flow velocity: 1.0mL/min;
Detect wavelength: 210nm;
Sample size: 20 μ L.
Carry out system suitability according to the method for embodiment 1, testing result is in table 2:
Table 2, mobile phase screening test result
| Numbering | Mobile phase | Retention time | Separating degree | Tailing factor | Theoretical cam curve |
| 1 | Methanol-water (25:75) | 25.935 | 21.123 | 0.999 | 49315 |
| 2 | Methanol-water (20:80) | 29.965 | 25.723 | 0.992 | 41278 |
| 3 | Methanol-water (30:70) | 22.771 | 18.756 | 0.987 | 78812 |
| 4 | Acetonitrile-water (20:80) | 26.759 | 22.828 | 0.976 | 75123 |
| 5 | Acetonitrile-water (25:75) | 28.223 | 25.022 | 0.961 | 67725 |
| 6 | Acetonitrile-water (30:70) | 19.712 | 15.157 | 1.002 | 99877 |
In table 2, mobile phase " for example: methanol-water (25:75) " has the implication that Chinese pharmacopoeia version in 2015 has conventionally, and wherein 85:15 represents the volume ratio of methyl alcohol and water; Retention time refers to the retention time of octylated diphenylamine; Separating degree refers to the separating degree between Lansoprazole and octylated diphenylamine; Tailing factor refers to the tailing factor of octylated diphenylamine chromatographic peak; Theoretical cam curve refers to theoretical cam curve (calculating by octylated diphenylamine chromatographic peak).
Result of the test shows, when mobile phase is methanol-water (20:80), methanol-water (25:75), methanol-water (30:70), acetonitrile-water (20:80), acetonitrile-water (25:75) and acetonitrile-water (30:70), be all suitable for detecting the content of octylated diphenylamine in Lansoprazole for injecting.
2, column temperature and flow velocity screening test
Select different column temperatures and flow velocity to carry out screening test, other chromatographic conditions are as follows:
The filler of chromatographic column: with octadecylsilane chemically bonded silica be filler;
The model of chromatographic column is WatersXbridgeshieldRP18, and specification is: internal diameter is 4.6mm, and length is 50mm, and filler particle diameter is 5 μ m;
Mobile phase: methanol-water (volume ratio is 25:75);
Column temperature: table 3;
Flow velocity: table 3;
Detect wavelength: 210nm;
Sample size: 20 μ L.
Carry out system suitability according to the method for embodiment 1, testing result is in table 3:
Table 3, column temperature and flow velocity screening test result
In table 3, retention time refers to the retention time of octylated diphenylamine; Separating degree refers to the separating degree between Lansoprazole and octylated diphenylamine; Tailing factor refers to the tailing factor of octylated diphenylamine; Theoretical cam curve refers to theoretical cam curve (calculating by octylated diphenylamine peak).
Result of the test shows, under different column temperature and flow velocity, the inventive method all can effectively accurately detect the content of octylated diphenylamine in Lansoprazole for injecting, and preferred column temperature is 35 DEG C～40 DEG C; Flow velocity is 0.8mL/min～1.0mL/min.
The methodology checking of embodiment 11 the inventive method
In methodology checking, chromatographic condition is all as follows:
The filler of chromatographic column: with octadecylsilane chemically bonded silica be filler;
The model of chromatographic column is WatersXbridgeshieldRP18, and specification is: internal diameter is 4.6mm, and length is 50mm, and filler particle diameter is 5 μ m;
Mobile phase: methanol-water (volume ratio is 25:75);
Column temperature: 40 DEG C;
Flow velocity: 1.0mL/min;
Detect wavelength: 210nm;
Sample size: 20 μ L.
1, linear relationship
Get reference substance (octylated diphenylamine), make the reference substance solution of a series of concentration in table 4 with mobile phase dilution. According to above-mentioned chromatographic condition, detect respectively, testing result is in table 4.
The testing result of table 4, linear relationship test
| Numbering | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Concentration (μ g/mL) | 0.615 | 1.23 | 2.46 | 4.92 | 9.84 | 19.68 | 49.2 |
| Peak area | 60223 | 123148 | 259682 | 521512 | 1096661 | 2212002 | 5588269 |
Taking the concentration x of octylated diphenylamine as abscissa, peak area y is ordinate, carries out linear regression, calculates regression equation and coefficient correlation, does linear relationship chart, and as shown in Figure 2, the regression equation of octylated diphenylamine is result: y=113953x-22873, R2＝1。
Result of the test shows: the concentration of octylated diphenylamine reference substance is within the scope of 0.615 μ g/mL～49.2 μ g/mL, and its concentration and peak area are good linear relationship.
2, specificity
Prepare need testing solution, reference substance solution the preparation mobile phase as solvent according to the inventive method.
Precision measures above-mentioned each solution 20 μ L injection liquid chromatographies, records chromatogram, sees Fig. 3-5:(a) need testing solution; (b) reference substance solution; (c) solvent blank solution.
Result of the test shows, the method that blank solution can not detect octylated diphenylamine content in Lansoprazole for injecting to RPLC of the present invention cause interference.
3, precision
Get octylated diphenylamine reference substance appropriate, accurately weighed, add mobile phase dissolving and quantitatively dilute and make the solution containing 0.5 μ g in every 1mL, product solution in contrast;
According to the chromatographic condition of test example 3, precision measures 20 μ L reference substance solution, injection liquid chromatography, and continuous sample introduction 6 times, records chromatogram.
Testing result is in table 5.
The testing result of table 5, precision test
Result of the test shows, the inventive method precision is good.
4, stability
Get Lansoprazole for injecting, be mixed with need testing solution and octylated diphenylamine reference substance solution according to the inventive method, get reference substance solution respectively at 0h, 2h, 4h, 6h, 8h, sample detection; According to the chromatographic condition of test example 3, precision measures 20 μ L reference substance solution, injection liquid chromatography, and the content by external standard method with SRS isomers in calculated by peak area test sample, the results are shown in Table 6.
The testing result of table 6, stability test
| Time (h) | 0 | 2 | 4 | 6 | 8 | RSD(％) |
| Octylated diphenylamine | 532255 | 530177 | 528335 | 533701 | 523210 | 0.77％ |
Result of the test shows, the inventive method has good stability.
5, repeatability
Get Lansoprazole for injecting, be mixed with need testing solution according to the inventive method, 6 parts of need testing solutions of parallel preparation respectively, and prepare octylated diphenylamine reference substance solution; Injection liquid chromatography respectively, the content by external standard method with octylated diphenylamine in calculated by peak area test sample, the results are shown in Table 7.
The testing result of table 7, replica test
| Sample | 1 | 2 | 3 | 4 | 5 | 6 |
| Octylated diphenylamine | Do not detect | Do not detect | Do not detect | Do not detect | Do not detect | Do not detect |
Result of the test shows, the inventive method is reproducible.
6, solvent interference test
Solvent interference test: measure 20 μ L mobile phase solution injection liquid chromatographies, record chromatogram, in blank solvent chromatogram with octylated diphenylamine corresponding position, occur without chromatographic peak.
Prepare need testing solution: claim Lansoprazole for injecting 25mg, be placed in 50mL measuring bottle, add mobile phase (methanol-water=25:75) and make to dissolve, as need testing solution.
Preparation reference substance solution: take reference substance (octylated diphenylamine) 5mg, be placed in 100mL measuring bottle, precision measures 1mL, be placed in 100mL measuring bottle, add mobile phase (methanol-water=25:75) and be diluted to scale, shake up, in contrast product solution.
Get reference substance solution 20 μ L, injection liquid chromatography, regulates detection sensitivity, make the peak height of octylated diphenylamine chromatographic peak be about 20% of recorder full scale, precision measures need testing solution and the each 20 μ L of reference substance solution again, and injection liquid chromatography, records chromatogram respectively. If show the chromatographic peak of octylated diphenylamine in the chromatogram of need testing solution, must not cross 0.1% by external standard method with the content of calculated by peak area octylated diphenylamine. According to above-mentioned method, Lansoprazole for injecting is detected 3 times.
Result of the test shows, does not detect octylated diphenylamine in test sample, and Lansoprazole for injecting and octylated diphenylamine reach good baseline separation.
7, quantitative limit and detectability
Take octylated diphenylamine reference substance 1.9219mg, be placed in 25mL measuring bottle, add mobile phase and dissolve and be settled to scale, shake up, in contrast product stock solution.
Preparation reference substance solution: measure the each 1.0mL of above-mentioned reference substance solution, be placed in 50mL measuring bottle, add mobile phase and dissolve and be settled to scale, shake up, then measure 2.5mL, be placed in 25mL measuring bottle, add mobile phase and be settled to scale, in contrast solution.
Measure above-mentioned reference substance solution 1.0mL, be placed in 25mL measuring bottle, add mobile phase and dissolve and be settled to scale, shake up, as the detection solution (S/N ≈ 10) of quantitative limit test.
Measure above-mentioned reference substance solution 3mL, be placed in 10mL measuring bottle, add mobile phase and dissolve and be settled to scale, shake up, as the detection solution (S/N ≈ 3) of detectability test.
What record octylated diphenylamine is quantitatively limited to 6.15ng/mL.
The detection that records octylated diphenylamine is limited to 1.85ng/mL.
8, the rate of recovery
Get 9 bottles of 130701 batches of Lansoprazole for injecting, add respectively octylated diphenylamine reference substance solution (concentration 1:3.936 μ g/mL; Concentration 2:4.92 μ g/mL; Concentration 3:5.904 μ g/mL; ) 5mL sample dissolution, each concentration is prepared 3 parts, fully shakes up, as need testing solution. And prepare reference substance solution according to the above-mentioned method of drafting, and accurate test sample and the reference substance solution 20 μ L sample introductions mensuration drawn, record chromatogram, and calculate respectively the amount of recording and the rate of recovery of octylated diphenylamine, and it the results are shown in Table 8.
Table 8 octylated diphenylamine recovery test result table
Above result of the test shows, measures octylated diphenylamine in Lansoprazole by the present invention's convenience, and its method rate of recovery is good, and relative standard deviation is little, meets the requirements.
In sum, the HPLC detection method of octylated diphenylamine in Lansoprazole of the present invention, octylated diphenylamine in Lansoprazole is separated and detected, testing result accurately, reliably, and there is the plurality of advantages such as linear relationship excellence, precision are high, good stability, reproducible, the rate of recovery good, easy and simple to handle, cost is low, quality that can effective monitoring Lansoprazole for injecting, is suitable for applying.
Claims (10)
1. the HPLC detection method of octylated diphenylamine in Lansoprazole, is characterized in that: it comprises the following steps:
A, prepare need testing solution:
Get Lansoprazole sample to be measured, mobile phase dissolves, and prepares need testing solution;
B, prepare the reference substance solution of octylated diphenylamine:
Get octylated diphenylamine reference substance, mobile phase dissolves, and prepares the reference substance solution of octylated diphenylamine;
C, respectively need testing solution and reference substance solution are injected to high performance liquid chromatograph and detect, chromatographic condition is as follows:
Chromatographic column: C18 chromatographic column;
Mobile phase: methanol-water or acetonitrile-water;
Detect wavelength: 210 ± 5nm, preferably detecting wavelength is 210 ± 2nm;
D, calculate the octylated diphenylamine content in Lansoprazole according to testing result.
2. HPLC detection method according to claim 1, is characterized in that: in step c, described chromatographic columnSpecification is: internal diameter 4.6mm, length 50mm, packing material size 5 μ m.
3. HPLC detection method according to claim 2, is characterized in that: in step c, described chromatographic columnModel is WatersXbridgeshieldRP18.
4. HPLC detection method according to claim 1, is characterized in that: in step c, described methanol-waterVolume ratio is 20%:80%～30%:70%; The volume ratio of acetonitrile-water is 20%:80%～30%:70%.
5. HPLC detection method according to claim 4, is characterized in that: in step c, described mobile phase isThe mixed solvent of following volume ratio:
Methanol-water=20:80, methanol-water=25:75, methanol-water=30:70, acetonitrile-water=20:80, acetonitrile-water=25:75 or acetonitrile-water=30:70.
6. HPLC detection method according to claim 1, is characterized in that: in step a, need testing solutionConcentration is 0.4～0.6mg/mL; In step b, the concentration of reference substance solution is 0.1～1.0 μ g/mL.
7. according to the HPLC detection method described in claim 1-6 any one, it is characterized in that: in step c, described inThe column temperature of chromatographic condition is 35 DEG C～45 DEG C, and preferred column temperature is 35 DEG C～40 DEG C; Flow velocity be 0.8mL/min～1.2mL/min, preferred flow velocity is 0.8mL/min～1.0mL/min.
8. according to the HPLC detection method described in claim 4-7 any one, it is characterized in that: in step c, described inThe volume ratio of methanol-water is 20%:80%～25%:75%; The volume ratio of acetonitrile-water is 20%:80%～25%:75%.
9. according to the HPLC detection method described in claim 1-8 any one, it is characterized in that: in step c, described inThe sample size of chromatographic condition is 20 μ L.
10. according to the HPLC detection method described in claim 1-9 any one, it is characterized in that: described Lansoprazole sampleProduct are Lansoprazole for injecting.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510981513.XA CN105606746B (en) | 2015-12-23 | 2015-12-23 | The HPLC detection methods of octylated diphenylamine in Lansoprazole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510981513.XA CN105606746B (en) | 2015-12-23 | 2015-12-23 | The HPLC detection methods of octylated diphenylamine in Lansoprazole |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105606746A true CN105606746A (en) | 2016-05-25 |
| CN105606746B CN105606746B (en) | 2017-10-17 |
Family
ID=55986841
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510981513.XA Active CN105606746B (en) | 2015-12-23 | 2015-12-23 | The HPLC detection methods of octylated diphenylamine in Lansoprazole |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105606746B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112834627A (en) * | 2019-11-22 | 2021-05-25 | 扬子江药业集团有限公司 | Method for separating and measuring lansoprazole related substances for injection by high performance liquid chromatography |
| CN115308323A (en) * | 2022-07-19 | 2022-11-08 | 山东新华鲁抗医药有限公司 | Method for measuring content of meglumine in lansoprazole for injection |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013078578A1 (en) * | 2011-11-28 | 2013-06-06 | 海南灵康制药有限公司 | Lansoprazole compound and novel preparation method thereof |
| CN104267130A (en) * | 2014-10-24 | 2015-01-07 | 湖北华世通潜龙药业有限公司 | Method for measuring impurities in lansoprazole and oral preparation by using HPLC (high performance liquid chromatography) |
| CN104483403A (en) * | 2014-12-05 | 2015-04-01 | 广东东阳光药业有限公司 | Method for detecting related substances of dexlansoprazole raw medicinal material |
| CN104634892A (en) * | 2015-01-27 | 2015-05-20 | 桂林华信制药有限公司 | Determination method for lanso chloride in lansoprazole |
-
2015
- 2015-12-23 CN CN201510981513.XA patent/CN105606746B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013078578A1 (en) * | 2011-11-28 | 2013-06-06 | 海南灵康制药有限公司 | Lansoprazole compound and novel preparation method thereof |
| CN104267130A (en) * | 2014-10-24 | 2015-01-07 | 湖北华世通潜龙药业有限公司 | Method for measuring impurities in lansoprazole and oral preparation by using HPLC (high performance liquid chromatography) |
| CN104483403A (en) * | 2014-12-05 | 2015-04-01 | 广东东阳光药业有限公司 | Method for detecting related substances of dexlansoprazole raw medicinal material |
| CN104634892A (en) * | 2015-01-27 | 2015-05-20 | 桂林华信制药有限公司 | Determination method for lanso chloride in lansoprazole |
Non-Patent Citations (3)
| Title |
|---|
| BAIMING XIAO等: "Development and validation of HPLC methods for the determination of potential extractables from elastomeric stoppers in the presence of a complex surfactant vehicle used in the preparation of parenteral drug products", 《JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS》 * |
| 杨艳等: "HPLC测定注射用兰索拉唑中兰索拉唑的含量和有关物质", 《中国药学杂志》 * |
| 缪玉山等: "RP-HPLC测定兰索拉唑制剂中主药及有关物质的含量", 《中国现代应用药学杂志》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112834627A (en) * | 2019-11-22 | 2021-05-25 | 扬子江药业集团有限公司 | Method for separating and measuring lansoprazole related substances for injection by high performance liquid chromatography |
| CN115308323A (en) * | 2022-07-19 | 2022-11-08 | 山东新华鲁抗医药有限公司 | Method for measuring content of meglumine in lansoprazole for injection |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105606746B (en) | 2017-10-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104483403B (en) | A kind of detect the method that R-lansoprazole bulk drug has related substance | |
| CN103592379B (en) | Analytic method of omeprazole related substance | |
| CN110646550A (en) | Method for detecting related substances in atorvastatin calcium | |
| CN104122363A (en) | Measuring method of mecobalamin tablet related substance | |
| CN102798678A (en) | Detection method and content determining method of sodium calcium edetate in pantoprazole sodium for injecting | |
| CN105044269A (en) | Method for detecting initial material II in apixaban through reversed-phase high performance liquid chromatography | |
| CN103063769B (en) | Quality detecting method for mecobalamine capsule | |
| CN105021728A (en) | Method for determination of contents of impurities in cefuroxime axetil raw material medicine by high performance liquid chromatography | |
| CN105021740A (en) | High-performance liquid chromatography analytical method for N1,N1-diisopropyl ethylenediamine | |
| CN105606746A (en) | HPLC (high-performance liquid chromatography) detection method for octylated diphenylamine in lansoprazole | |
| CN113125583B (en) | Method for detecting content of genotoxic impurities in pantoprazole sodium for injection | |
| CN105467021A (en) | Method for separation determination of related substances in bulk drugs and preparations of paricalcitol through HPLC method | |
| CN104730165A (en) | High performance liquid chromatography (HPLC) detection method of Rivaroxaban | |
| CN108398497B (en) | High performance liquid chromatography detection method of tris (nonylphenol) phosphite ester | |
| CN104730194B (en) | The detection method of bilastine | |
| CN104764840B (en) | The separation of palonosetron Hcl and impurity and detection method | |
| CN108445101B (en) | Method for detecting related substances of risperidone oral solution | |
| CN104950053A (en) | Method for measuring content of impurities in cefuroxime axetil tablet through high performance liquid chromatography | |
| CN103063794B (en) | Content detecting and control method of epalrestat tablets | |
| CN105548393A (en) | Method for detecting content of impurity in apremilast raw material | |
| CN105486785A (en) | Method for detecting enantiomer impurity in apremilast | |
| CN101661019A (en) | Method for separating and measuring Palonosetron hydrochloride and optical isomers thereof | |
| CN104101663A (en) | Method for testing ebastine-related substances by high performance liquid chromatography | |
| CN104678006B (en) | A kind of Sunitinib malate Related substance method | |
| CN102636597A (en) | Method for measuring residual solvent in tetracycline hydrochloride bulk drug by utilizing headspace gas chromatography |
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 | ||
| CP03 | Change of name, title or address |
Address after: No. 343 Hezuo Road, Chengdu High tech Zone, Chengdu, Sichuan Province, 611730 Patentee after: Sichuan Hongming Bosi Pharmaceutical Co.,Ltd. Address before: No. 1002, Building 11, No. 88, South Keyuan Road, Hi tech Zone, Chengdu, Sichuan 610000 Patentee before: CHENGDU BAIYU GINKGOLIDE PHARMACEUTICALS Co.,Ltd. |
|
| CP03 | Change of name, title or address |