CN104020230B - Method for detecting by-product in penehyclidine hydrochloride - Google Patents
Method for detecting by-product in penehyclidine hydrochloride Download PDFInfo
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Abstract
The invention discloses a method for detecting a by-product in penehyclidine hydrochloride. The detecting method comprises the following steps of detecting the content of the by-product in penehyclidine hydrochloride by using a high-efficiency liquid chromatography, wherein the by-product is 3-[2-cyclopentyl2-phenyl-2-(2-cyclopentyl-2-hydroxy-2-phenyl-ethyoxyl)-ethyoxyl]; preparing a test solution for later use, preparing a reference substance solution for later use, and measuring the test solution and the reference substance solution. The method provided by the invention has the advantages that the detection limit of the device can achieve 0.32mug/ml, 3-[2-cyclopentyl2-phenyl-2-(2-cyclopentyl-2-hydroxy-2-phenyl-ethyoxyl)-ethyoxyl]quinine naphthene hydrochloride which is higher than 0.03% in a hydrochloric acid penehyclidine hydrochloride original soup is detected, and a practical detecting effect is good.
Description
Technical field
The present invention is a kind of method for detecting accessory substance in amyl ethyl quin ether hydrochloride, is specifically related to the quantitative detecting method of accessory substance in amyl ethyl quin ether hydrochloride bulk drug, belongs to drug tests.
Background technology
Amyl ethyl quin ether hydrochloride is the new drug with independent intellectual property right of China's development, the existing formulation of its bulk drug is mainly parenteral solution, i.e. penehyclidine hydrochloride injection (long holder is peaceful), there is selectivity choline receptor antagonism, the bad reactions such as the tachycardia that can not only effectively avoid atropine to produce, also there is drug effect long, the advantages such as bad reaction is few, its indication comprises: for preanesthetic medication to suppress salivary gland and air flue glandular secretion, for the treatment of organophosphorus poison (agricultural chemicals) poisoning first-aid and poisoning later stage or cholinesterase (ChE) aging rear maintenance atropinization etc.At present, this medicine has started application in the clinical fields such as preanesthetic medication, organic phosphorus pesticide poisoning rescue, shock, respiratory disease, angiocardiopathy and drug addiction treatment, the application etc. of amyl ethyl quin ether hydrochloride in preparation treatment haemorrhagic shock medicine that the application of the amyl ethyl quin ether hydrochloride that a kind of medical compounds disclosed as: patent documentation CN02134118.4 and composition thereof and the application in pharmacy, patent documentation CN200510088052.X disclose in pharmacy and patent documentation CN200910058142.2 disclose.
Existing situation is, along with the increasingly stringent of requirement is studied with clear and definite to impurity in drug research and development by China, especially the research of medicine accessory substance, catabolite etc. has been entered to the today in a brand-new stage, whether medicine can produce bad reaction in Clinical practice becomes more and more important.Certainly, we also clearly know, in actual clinical field, the bad reaction that medicine produces in Clinical practice process, outside the Pass having with the pharmacologically active of medicine major component, also there is relation with the impurity that exists in medicine, in clinical trial, mode often through medicine accessory substance exists, therefore, for improving constantly security and the validity of penehyclidine hydrochloride injection, the present invention establishes a kind of method that energy accurate quantitative analysis detects the accessory substance in amyl ethyl quin ether hydrochloride (as: amyl ethyl quin ether hydrochloride original liquid).
Summary of the invention
The object of the present invention is to provide a kind of method for detecting accessory substance in amyl ethyl quin ether hydrochloride, this detection method adopts high performance liquid chromatography, with 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride in contrast product position, to the quantitative detection that 3-in amyl ethyl quin ether hydrochloride [2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride carries out, its specificity, quantitative limit and detectability, linearly, precision, accuracy, stability of solution, the aspects such as durability are all through detailed certification, and every the result all meets the requirement of relevant laws and regulations and governing principle, actual Detection results is good.
The present invention is achieved through the following technical solutions: a kind of method for detecting accessory substance in amyl ethyl quin ether hydrochloride, described detection method comprises the content using high performance liquid chromatography to detect accessory substance in amyl ethyl quin ether hydrochloride, described accessory substance is 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride, comprises following steps:
A: prepare need testing solution: get amyl ethyl quin ether hydrochloride and mobile phase is hybridly prepared into need testing solution, stand-by, in mass ratio, amyl ethyl quin ether hydrochloride: the ratio of mobile phase is (1 ~ 3): 1000;
B: preparation reference substance solution: 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride reference substance is provided, 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride reference substance and mobile phase are hybridly prepared into reference substance solution, stand-by, count in mass ratio, 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride reference substance: the ratio of mobile phase is (0.005 ~ 0.02): 1000,
C: measure: the reference substance solution of difference draws equal amounts and need testing solution, inject high performance liquid chromatograph and measure, the condition determination of described high performance liquid chromatography comprises:
Chromatographic column: take octadecyl silane as filling agent;
Mobile phase: primarily of methanol-water phase or acetonitrile-water phase composition;
Flow velocity: 0.5 ~ 1.5ml/min;
Column temperature: 20 ~ 40 DEG C;
Determined wavelength: 205 ~ 216nm.
This method detectability reaches 0.62 μ g/ml, namely can detect 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride higher than 0.03% in amyl ethyl quin ether hydrochloride, practical.
For realizing above-mentioned steps better, further in described steps A, the mass ratio of amyl ethyl quin ether hydrochloride and mobile phase is 2:1000; In described step B, the mass ratio of 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride reference substance and mobile phase is 0.01:1000.
In the present invention, described mobile phase is: volume ratio is the methyl alcohol-0.02mol/L potassium dihydrogen phosphate-triethylamine of 80:20:0.5.
Further, described mobile phase phosphoric acid solution adjust ph is 4.0 ~ 6.0.
In actual testing process, for the high performance liquid chromatography that the present invention adopts, in its condition determination, each parameter is after suitably adjusting, all can accurately detect the content of 3-in amyl ethyl quin ether hydrochloride [2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride, comprise the adjustment that mobile phase pH value, flow velocity, column temperature and determined wavelength are carried out, as follows:
(1) in described step C, in high effective liquid chromatography for measuring condition, the pH value of mobile phase is 4.0,5.0 or 6.0.
(2) in described step C, the flow velocity in high effective liquid chromatography for measuring condition is 0.5ml/min, 1.0ml/min or 1.5ml/min.
(3) in described step C, the column temperature in high effective liquid chromatography for measuring condition is 25 DEG C, 35 DEG C or 40 DEG C.
(4) in described step C, the determined wavelength in high effective liquid chromatography for measuring condition is 205 nm, 210 nm or 216 nm.
The present invention compared with prior art, has the following advantages and beneficial effect:
(1) the present invention is the quantitative detection to accessory substance 3-in amyl ethyl quin ether hydrochloride [2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride, principle is very simple, adopt high performance liquid chromatography, with 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride in contrast product position, its specificity, quantitative limit and detectability, linearly, precision, accuracy, stability of solution, the aspects such as durability are all through detailed certification, and every the result all meets the requirement of relevant laws and regulations and governing principle, actual Detection results is good.
(2) the present invention is practical, in actual testing process, its detectability can reach 0.62 μ g/ml, namely can detect the content higher than 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride of 0.03% in amyl ethyl quin ether hydrochloride, testing process is simple, quick.
(3) high performance liquid chromatography of the present invention, the scope that its condition determination comprises is effective value, that is: after getting arbitrary value in each parameter area, also the content of 3-in amyl ethyl quin ether hydrochloride [2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride can accurately be detected, in actual testing process, be convenient to detection person to the adjustment of parameter and the impact of avoiding human error to produce testing result, suitablely extensively promote the use of.
Accompanying drawing explanation
Fig. 1 is the chemical formula of amyl ethyl quin ether hydrochloride of the present invention.
Fig. 2 is the chemical formula of 3-of the present invention [2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride.
Fig. 3 is the liquid chromatogram of reference substance solution of the present invention.
Fig. 4 is the liquid chromatogram of need testing solution of the present invention.
Embodiment
Below goal of the invention of the present invention, technical scheme and beneficial effect are described in further detail.
It should be noted that, it is all exemplary for below describing in detail, be intended for the requested to provide further explanation of the invention, except as otherwise noted, all technology used herein and scientific terminology have the identical meanings usually understood with general technical staff of the technical field of the invention.
For constantly improving security and the validity of amyl ethyl quin ether hydrochloride medicine, the present invention proposes a kind of method for detecting accessory substance in amyl ethyl quin ether hydrochloride, mainly to the quantitative detection of accessory substance 3-in amyl ethyl quin ether hydrochloride [2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride, the method is through detailed Method validation, there is good use value, its checking content includes: specificity, quantitative limit and detectability, linearly, precision, accuracy, stability of solution, durability etc., and every the result all meets the requirement of relevant laws and regulations and governing principle.In actual testing process, the detectability of this method can reach 0.62 μ g/ml, namely can detect 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride higher than 0.03% in amyl ethyl quin ether hydrochloride, actual Detection results is good.
Below further describing technical solution of the present invention:
This detection method uses high performance liquid chromatography to the quantitative detection of accessory substance 3-in amyl ethyl quin ether hydrochloride [2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride, wherein, the chemical formula of amyl ethyl quin ether hydrochloride and accessory substance 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride is respectively as Fig. 1, shown in Fig. 2, the high performance liquid chromatography that the present invention uses be then adopt 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride in contrast product position, 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride in amyl ethyl quin ether hydrochloride is detected, concrete operation step can be summarized as follows:
A: prepare need testing solution: get amyl ethyl quin ether hydrochloride and mobile phase is hybridly prepared into need testing solution, stand-by, in mass ratio, amyl ethyl quin ether hydrochloride: the ratio of mobile phase is (1 ~ 3): 1000, optimization, and its ratio is 2:1000;
B: preparation reference substance solution: 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride reference substance is provided, 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride reference substance and mobile phase are hybridly prepared into reference substance solution, stand-by, count in mass ratio, 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride reference substance: the ratio of mobile phase is (0.005 ~ 0.02): 1000, optimize, its ratio is 0.01:1000,
C: measure: the reference substance solution of difference draws equal amounts and need testing solution, inject high performance liquid chromatograph and measure, the condition determination of described high performance liquid chromatography comprises:
Chromatographic column: take octadecyl silane as filling agent;
Mobile phase: primarily of methanol-water phase or acetonitrile-water phase composition;
Flow velocity: 0.5 ~ 1.5ml/min;
Column temperature: 20 ~ 40 DEG C;
Determined wavelength: 205 ~ 216nm.
In actual testing process, for the high performance liquid chromatography that the present invention adopts, in its condition determination, each parameter is after suitably adjusting, all can accurately detect the content of 3-in amyl ethyl quin ether hydrochloride [2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride, comprise mobile phase pH value, flow velocity, the adjustment etc. that column temperature and determined wavelength carry out, therefore, explanation the specific embodiment of the present invention is enumerated below with nine exemplary embodiments, the amyl ethyl quin ether hydrochloride that each embodiment all chooses different lot number detects, certainly, protection scope of the present invention is not limited to following examples.
Embodiment 1:
Choose the amyl ethyl quin ether hydrochloride that lot number is 080601, the content of its accessory substance 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride is detected, as follows:
A: prepare need testing solution: add 25ml pH value 5.0 in the amyl ethyl quin ether hydrochloride of 50mg, methyl alcohol-0.02mol/L potassium dihydrogen phosphate-triethylamine that volume ratio is 80:20:0.5, its mass ratio is 2:1000, after mixing, be mixed with the solution of the hydrochloric amyl ethyl quin ether 2mg of every 1ml, as need testing solution, stand-by;
B: preparation reference substance solution: add 10ml pH value 5.0 in 100 μ g 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride reference substance, methyl alcohol-0.02mol/L potassium dihydrogen phosphate-triethylamine that volume ratio is 80:20:0.5, its mass ratio 0.01:1000, after mixing, be mixed with the solution of every 1ml containing 10.0 μ g, product solution, stand-by in contrast;
C: measure: draw reference substance solution and each 10 μ l of need testing solution respectively, inject high performance liquid chromatograph to measure, Fig. 3 and Fig. 4 is respectively the liquid chromatogram of 3-of the present invention [2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride reference substance solution and amyl ethyl quin ether hydrochloride need testing solution, wherein, the condition determination of high performance liquid chromatography comprises:
Chromatographic column: take octadecyl silane as filling agent;
Mobile phase: pH value 5.0, volume ratio are the methyl alcohol-0.02mol/L potassium dihydrogen phosphate-triethylamine of 80:20:0.5;
Flow velocity: 1.0ml/min;
Column temperature: 35 DEG C;
Determined wavelength: 210nm.
Known after testing, lot number is the content of accessory substance 3-in 080601 batch of amyl ethyl quin ether hydrochloride [2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride is 0.162%.
Embodiment 2:
The present embodiment is only from the difference of embodiment 1: in chromatographic condition the parameter of flow velocity and the amyl ethyl quin ether hydrochloride lot number chosen different.
In the present embodiment, the amyl ethyl quin ether hydrochloride lot number chosen is 090901, when detecting the content of its accessory substance 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride, the condition determination of high performance liquid chromatography comprises:
Chromatographic column: take octadecyl silane as filling agent;
Mobile phase: methyl alcohol-0.02mol/L potassium dihydrogen phosphate-triethylamine that pH value is 5.0, volume ratio is 80:20:0.5;
Flow velocity: 1.5ml/min;
Column temperature: 35 DEG C;
Determined wavelength: 210nm.
Known after testing, lot number is the content of accessory substance 3-in the amyl ethyl quin ether hydrochloride of 090901 [2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride is 0.188%.
Embodiment 3:
The present embodiment is only from the difference of embodiment 1: in chromatographic condition the parameter of flow velocity and the amyl ethyl quin ether hydrochloride lot number chosen different.
In the present embodiment, the amyl ethyl quin ether hydrochloride lot number chosen is 100701, when detecting the content of its accessory substance 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride, the condition determination of high performance liquid chromatography comprises:
Chromatographic column: take octadecyl silane as filling agent;
Mobile phase: methyl alcohol-0.02mol/L potassium dihydrogen phosphate-triethylamine that pH value is 5.0, volume ratio is 80:20:0.5;
Flow velocity: 0.5ml/min;
Column temperature: 35 DEG C;
Determined wavelength: 210nm.
Known after testing, lot number is the content of accessory substance 3-in the amyl ethyl quin ether hydrochloride of 100701 [2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride is 0.080%.
Embodiment 4:
The present embodiment is from the difference of embodiment 1: in chromatographic condition the parameter of column temperature and the amyl ethyl quin ether hydrochloride lot number chosen different.
In the present embodiment, the amyl ethyl quin ether hydrochloride lot number chosen is 111101, when detecting the content of its accessory substance 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride, the condition determination of high performance liquid chromatography comprises:
Chromatographic column: take octadecyl silane as filling agent;
Mobile phase: methyl alcohol-0.02mol/L potassium dihydrogen phosphate-triethylamine that pH value is 5.0, volume ratio is 80:20:0.5;
Flow velocity: 1.0ml/min;
Column temperature: 25 DEG C;
Determined wavelength: 210nm.
Known after testing, lot number is the content of accessory substance 3-in the amyl ethyl quin ether hydrochloride of 111101 [2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride is 0.071%.
Embodiment 5:
The present embodiment is from the difference of embodiment 1: in chromatographic condition the parameter of column temperature and the amyl ethyl quin ether hydrochloride lot number chosen different.
In the present embodiment, the amyl ethyl quin ether hydrochloride lot number chosen is 120201, when detecting the content of its accessory substance 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride, the condition determination of high performance liquid chromatography comprises:
Chromatographic column: take octadecyl silane as filling agent;
Mobile phase: methyl alcohol-0.02mol/L potassium dihydrogen phosphate-triethylamine that pH value is 5.0, volume ratio is 80:20:0.5;
Flow velocity: 1.0ml/min;
Column temperature: 40 DEG C;
Determined wavelength: 210nm.
Known after testing, lot number is the content of accessory substance 3-in the amyl ethyl quin ether hydrochloride of 120201 [2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride is 0.134%.
Embodiment 6:
The present embodiment is from the difference of embodiment 1: in chromatographic condition the pH value of mobile phase and the amyl ethyl quin ether hydrochloride lot number chosen different.
In the present embodiment, the amyl ethyl quin ether hydrochloride lot number chosen is 120901, when detecting the content of its accessory substance 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride, the condition determination of high performance liquid chromatography comprises:
Chromatographic column: take octadecyl silane as filling agent;
Mobile phase: methyl alcohol-0.02mol/L potassium dihydrogen phosphate-triethylamine that pH value is 4.0, volume ratio is 80:20:0.5;
Flow velocity: 1.0ml/min;
Column temperature: 40 DEG C;
Determined wavelength: 210nm.
Known after testing, lot number is the content of accessory substance 3-in the amyl ethyl quin ether hydrochloride of 120901 [2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride is 0.065%.
Embodiment 7:
The present embodiment is from the difference of embodiment 1: in chromatographic condition the pH value of mobile phase and the amyl ethyl quin ether hydrochloride lot number chosen different.
In the present embodiment, the amyl ethyl quin ether hydrochloride lot number chosen is 130701, when detecting the content of its accessory substance 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride, the condition determination of high performance liquid chromatography comprises:
Chromatographic column: take octadecyl silane as filling agent;
Mobile phase: methyl alcohol-0.02mol/L potassium dihydrogen phosphate-triethylamine that pH value is 6.0, volume ratio is 80:20:0.5;
Flow velocity: 1.0ml/min;
Column temperature: 40 DEG C;
Determined wavelength: 210nm.
Known after testing, lot number is the content of accessory substance 3-in the amyl ethyl quin ether hydrochloride of 130701 [2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride is 0.0%.
Embodiment 8:
The present embodiment is from the difference of embodiment 1: in chromatographic condition the parameter of determined wavelength and the amyl ethyl quin ether hydrochloride lot number chosen different.
In the present embodiment, the amyl ethyl quin ether hydrochloride lot number chosen is 131101, when detecting the content of its accessory substance 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride, the condition determination of high performance liquid chromatography comprises:
Chromatographic column: take octadecylsilane chemically bonded silica as filling agent;
Mobile phase: methyl alcohol-0.02mol/L potassium dihydrogen phosphate-triethylamine that pH value is 5.0, volume ratio is 80:20:0.5;
Flow velocity: 1.0ml/min;
Column temperature: 40 DEG C;
Determined wavelength: 205nm.
Known after testing, lot number is the content of accessory substance 3-in the amyl ethyl quin ether hydrochloride of 131101 [2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride is 0.044%.
Embodiment 9:
The present embodiment is from the difference of embodiment 8: in chromatographic condition, the parameter of determined wavelength is different.
In the present embodiment, the amyl ethyl quin ether hydrochloride lot number chosen is 131101, when detecting the content of its accessory substance 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride, the condition determination of high performance liquid chromatography comprises:
Chromatographic column: take octadecylsilane chemically bonded silica as filling agent;
Mobile phase: methyl alcohol-0.02mol/L potassium dihydrogen phosphate-triethylamine that pH value is 5.0, volume ratio is 80:20:0.5;
Flow velocity: 1.0ml/min;
Column temperature: 40 DEG C;
Determined wavelength: 216nm.
Known after testing, the content of accessory substance 3-in amyl ethyl quin ether hydrochloride [2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride is 0.045%.
The testing result of above-described embodiment 1 ~ 9 is added up, as illustrated in chart 1:
Table 1
| Numbering | Amyl ethyl quin ether hydrochloride lot number | The content (%) of impurity 3-quinuclidinol |
| 1 | 080601 | 0.162 |
| 2 | 090901 | 0.188 |
| 3 | 100701 | 0.080 |
| 4 | 111101 | 0.071 |
| 5 | 120201 | 0.134 |
| 6 | 120901 | 0.065 |
| 7 | 130701 | 0.0 |
| 8 | 131101 | 0.044 |
| 9 | 131101 | 0.045 |
From above-mentioned table 1, in amyl ethyl quin ether hydrochloride accessory substance 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride quantitative testing process in, each parameter suitably to chromatographic condition, after the pH value of: mobile phase, flow velocity, column temperature and determined wavelength adjust, its testing result is all effective, and its measurement result is accurately.
The above is only preferred embodiment of the present invention, and not do any pro forma restriction to the present invention, every any simple modification, equivalent variations done above embodiment according to technical spirit of the present invention, all falls within protection scope of the present invention.
Claims (5)
1. one kind for detecting the method for accessory substance in amyl ethyl quin ether hydrochloride, it is characterized in that: described detection method comprises the content using high performance liquid chromatography to detect accessory substance in amyl ethyl quin ether hydrochloride, described accessory substance is 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride, comprises following steps:
A: prepare need testing solution: get amyl ethyl quin ether hydrochloride and mobile phase is hybridly prepared into need testing solution, stand-by, in mass ratio, amyl ethyl quin ether hydrochloride: the ratio of mobile phase is (1 ~ 3): 1000;
B: preparation reference substance solution: 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride reference substance is provided, 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride reference substance and mobile phase are hybridly prepared into reference substance solution, stand-by, count in mass ratio, 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride reference substance: the ratio of mobile phase is (0.005 ~ 0.02): 1000,
C: measure: the reference substance solution of difference draws equal amounts and need testing solution, inject high performance liquid chromatograph and measure, the condition determination of described high performance liquid chromatography comprises:
Chromatographic column: take octadecyl silane as filling agent;
Mobile phase: volume ratio is the methyl alcohol-0.02mol/L potassium dihydrogen phosphate-triethylamine of 80:20:0.5;
Flow velocity: 0.5ml/min, 1.0ml/min or 1.5ml/min;
Column temperature: 25 DEG C, 35 DEG C or 40 DEG C;
Determined wavelength: 205 nm, 210 nm or 216 nm.
2. a kind of method for detecting accessory substance in amyl ethyl quin ether hydrochloride according to claim 1, is characterized in that: in described steps A, and the mass ratio of amyl ethyl quin ether hydrochloride and mobile phase is 2:1000.
3. a kind of method for detecting accessory substance in amyl ethyl quin ether hydrochloride according to claim 1, it is characterized in that: in described step B, the mass ratio of 3-[2-cyclopentyl 2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-Phenyl-ethoxy) ethoxy] quinuclidine hydrochloride reference substance and mobile phase is 0.01:1000.
4. a kind of method for detecting accessory substance in amyl ethyl quin ether hydrochloride according to claim 1, is characterized in that: described mobile phase phosphoric acid solution adjust ph is 4.0 ~ 6.0.
5. a kind of method for detecting accessory substance in amyl ethyl quin ether hydrochloride according to claim 4, is characterized in that: in described step C, and in high effective liquid chromatography for measuring condition, the pH value of mobile phase is 4.0,5.0 or 6.0.
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| WO2012142329A1 (en) * | 2011-04-12 | 2012-10-18 | Myrexis, Inc. | Compositions and therapeutic uses of ikk-related kinase epsilon and tankbinding kinase 1 inhibitors |
| CN103483333A (en) * | 2012-09-25 | 2014-01-01 | 成都自豪药业有限公司 | Crystal form of penehyclidine hydrochloride racemic mixture I and preparation method thereof |
-
2014
- 2014-06-20 CN CN201410277946.2A patent/CN104020230B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012142329A1 (en) * | 2011-04-12 | 2012-10-18 | Myrexis, Inc. | Compositions and therapeutic uses of ikk-related kinase epsilon and tankbinding kinase 1 inhibitors |
| CN103483333A (en) * | 2012-09-25 | 2014-01-01 | 成都自豪药业有限公司 | Crystal form of penehyclidine hydrochloride racemic mixture I and preparation method thereof |
Non-Patent Citations (4)
| Title |
|---|
| HPLC法测定富马酸 ( R, R" )-戊乙奎醚原料药及其有关物质的含量;王旭光等;《中国新药杂志》;20111231;第20卷(第8期);第748-750,760页 * |
| LC-MS-MS Determination or (S,R)-penehyclidine in Rat Plasma;Changkun Li等;《Chromatographia》;20100630;第71卷(第11/12期);第1025-1030页 * |
| 国家食品药品监督管理局.盐酸戊乙奎醚WS1-(X-026)-2004Z.《国家食品药品监督管理局国家药品标准》.2004, * |
| 魏君等.高效液相色谱手性流动相添加剂法测定富马酸( R,R)-戊乙奎醚中 3 个光学异构体杂质的含量.《中国药学杂志》.2013,第48卷(第2期),第136-139页. * |
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