阅读说明：本技术 一种盐酸环苯扎林中氯离子含量的检测方法 (Method for detecting chloride ion content in cyclobenzaprine hydrochloride ) 是由 徐志红 陆春晓 顾春香 胡成松 于 2021-09-09 设计创作，主要内容包括：本发明提供一种盐酸环苯扎林中氯离子含量的检测方法。所述盐酸环苯扎林中氯离子含量的检测方法包括以下步骤：(1)供试样品配制：将盐酸环苯扎林、硝酸、非离子型表面活性剂和水混合,得到供试样品溶液；(2)电位滴定分析：采用硝酸银溶液对所述供试样品溶液进行滴定,通过计算得出氯离子含量。本发明采用电位滴定法分析供试品,通过电位变化确定滴定终点。本发明具有准确度高、分析快速、抗干扰性强,和灵敏度高的优点。(The invention provides a method for detecting the content of chloride ions in cyclobenzaprine hydrochloride. The method for detecting the content of chloride ions in cyclobenzaprine hydrochloride comprises the following steps: (1) preparing a test sample: mixing cyclobenzaprine hydrochloride, nitric acid, a non-ionic surfactant and water to obtain a sample solution; (2) potentiometric titration analysis: and titrating the test sample solution by using a silver nitrate solution, and calculating to obtain the content of chloride ions. The invention adopts a potentiometric titration method to analyze a sample to be tested and determines a titration end point through the change of the potential. The invention has the advantages of high accuracy, rapid analysis, strong anti-interference performance and high sensitivity.)

1. A method for detecting the content of chloride ions in cyclobenzaprine hydrochloride is characterized by comprising the following steps:

(1) preparing a test sample: mixing cyclobenzaprine hydrochloride, nitric acid, a non-ionic surfactant and water to obtain a sample solution;

(2) potentiometric titration analysis: and titrating the test sample solution by using a silver nitrate solution, and calculating to obtain the content of chloride ions.

2. The method for detecting the content of chloride ions in the ciclopirox hydrochloride according to claim 1, wherein in the step (1), the test sample solution comprises the following components in percentage by mass: 0.05-0.3% of cyclobenzaprine hydrochloride, 0.5-3% of nitric acid, 0.05-5% of nonionic surfactant and 90-99% of water.

3. The method for detecting the content of chloride ions in the ciclopirox hydrochloride according to claim 1 or 2, characterized in that in the step (1), the non-ionic surfactant comprises any one or a combination of at least two of triton X-100, polyethylene glycol or polyvinylpyrrolidone, preferably the combination of triton X-100.

4. The method for detecting the content of chloride ions in the ciclopirox hydrochloride according to any one of claims 1 to 3, wherein in the step (1), the concentration of the nitric acid is 14.4 to 15.2 mol/L.

5. The method for detecting the content of chloride ions in the ciclopirox hydrochloride according to any one of claims 1 to 4, wherein in the step (1), the specific steps of the preparation of the test sample are as follows: firstly, cyclobenzaprine hydrochloride is mixed with water, then nitric acid and nonionic surfactant are added, and stirring is carried out, so as to obtain the sample solution.

6. The method for detecting the content of chloride ions in the ciclopirox hydrochloride according to any one of claims 1 to 5, wherein in the step (2), the concentration of the silver nitrate solution is 0.05 to 0.2mol/L, preferably 0.1 mol/L.

7. The method for detecting the content of chloride ions in the ciclopirox hydrochloride according to any one of claims 1 to 6, characterized in that in the step (2), the electrode used for titration is a composite silver-plated platinum ring electrode;

preferably, the model of the composite silver-plated platinum ring electrode is DMi 141-SC;

preferably, in the step (2), the titration is performed by using a Mettler potentiometric titrator T50.

8. The method for detecting the chloride ion content in the ciclopirox hydrochloride according to any one of the claims 1 to 7, wherein in the step (2), the titrated reference electrolyte is a potassium nitrate solution;

preferably, the concentration of the potassium nitrate solution is 0.5-2mol/L, preferably 1 mol/L.

9. The method for detecting the content of chloride ions in the ciclopirox hydrochloride according to any one of claims 1 to 8, wherein the titration is performed under stirring, and the rotation speed of the stirring is 20 to 50 percent;

preferably, in step (2), the endpoint recognition threshold for the titration is in the range of 80-150mV/mL, preferably 100 mV/mL.

10. The method for detecting the chloride ion content of cyclobenzaprine hydrochloride according to any one of claims 1-9, wherein the method for detecting the chloride ion content of cyclobenzaprine hydrochloride comprises the following steps:

(1) preparing a test sample: firstly, mixing cyclobenzaprine hydrochloride with water, then adding nitric acid and a nonionic surfactant, and stirring to obtain a sample solution to be tested;

the test sample solution comprises the following components in percentage by mass: 0.05-0.3% of cyclobenzaprine hydrochloride, 1-3% of nitric acid, 0.05-5% of nonionic surfactant and 90-99% of water;

(2) potentiometric titration analysis: titrating the sample solution to be tested by using 0.05-0.2mol/L silver nitrate solution, and calculating to obtain the content of chloride ions;

wherein the electrode is a composite silver ring intelligent electrode DMi141-SC, the reference electrolyte is 0.5-2mol/L potassium nitrate solution, the stirring rotating speed is 20-50%, and the endpoint recognition threshold value is 50-150 mV/mL.

Technical Field

The invention belongs to the technical field of chemical analysis, and particularly relates to a method for detecting the content of chloride ions in cyclobenzaprine hydrochloride.

Background

Chloride ion is a common inorganic anion, but a certain harm is generated when the concentration is too high, so that the control of the content of the chloride ion is an important item in the quality control of the raw material medicaments. Chloride ions are commonly detected by four methods: (1) silver nitrate titration; (2) mercuric nitrate titration; (3) potentiometric titration; (4) ion chromatography. The method (3) is suitable for measuring colored and turbid liquid, a composite silver ring intelligent electrode is used as an electrode, and a silver nitrate standard solution is used as a titrant. In the titration process, the chloride ion concentration is continuously changed along with the continuous addition of the titrant, the potential of the electrode is correspondingly changed, the ion concentration is suddenly changed near a stoichiometric point, the potential of the electrode is suddenly changed, and the endpoint is determined.

CN112986163A discloses a chloride ion concentration detection method based on spectral analysis, and belongs to the technical field of chloride ion detection. The method is a high-stability detection reagent which is composed of a microemulsion consisting of n-butyl alcohol, triton, cyclohexane and deionized water, a nitric acid reagent and a silver nitrate solution, and a silver chloride suspension formed by a chloride ion solution to be detected and the high-stability detection reagent has special light absorption characteristics. The method is used for measuring the concentration of chloride ions in the solution by using a relation model between the content of chloride ions in the suspension and the absorbance, but the method is not suitable for measuring the content of chloride ions in cyclobenzaprine hydrochloride.

CN109212002A discloses a method for detecting chloride ions in nicotinic acid by potentiometric titration, which comprises the following steps: weighing a nicotinic acid sample into a beaker, adding deionized water, dissolving in ultrasonic waves, filtering by using medium-speed qualitative filter paper into a volumetric flask, and shaking up at constant volume; transferring 50mL of sample liquid from a measuring flask to a beaker, adding 0.5mL of nitric acid solution, placing a rotor and fixing the rotor on a magnetic stirrer, adjusting an acidity meter to a potential level, taking a silver electrode as an indicating electrode, taking a double-salt bridge saturated calomel electrode as a reference electrode, titrating by using a silver nitrate standard solution, recording a consumed volume V and a potential value E every 0.05-0.1mL, and finishing the titration when the potential is indicated to 350 ℃; this method has a problem that a precipitate adheres to an electrode during titration, thereby causing interference with measurement.

CN112557583A discloses a method for measuring the content of chloride ions in an additive by potentiometric titration. The method specifically comprises the following steps: mixing 1-5g of the admixture with 5-10mL of nitric acid solution, 100-300mL of deionized water and 0.5-1mL of glycol solution, and then ultrasonically dissolving for 5-10 min; adding a starch solution, taking a silver electrode as an indicating electrode and a calomel electrode as a reference electrode, adding sodium chloride standard solution with the same volume twice, titrating with silver nitrate solution under the stirring condition to the end point, and respectively obtaining the volume of the consumed silver nitrate solution at the end point of the titration twice; obtaining the volume of the consumed silver nitrate solution and the concentration of the silver nitrate solution at the end point of two titrations through blank test titration; calculating to obtain the content of chloride ions in the additive; this method has a problem that a precipitate adheres to an electrode during titration, thereby causing interference with measurement.

Therefore, the development of a method for ensuring rapid and efficient determination of chloride ions in cyclobenzaprine hydrochloride is an important research point in the field of pharmaceutical analysis.

Disclosure of Invention

Aiming at the defects of the prior art, the invention aims to provide a method for detecting the content of chloride ions in cyclobenzaprine hydrochloride. The detection method has the characteristics of high accuracy, quick analysis, strong anti-interference performance and high sensitivity.

In order to achieve the purpose, the invention adopts the following technical scheme:

in a first aspect, the invention provides a method for detecting the chloride ion content in cyclobenzaprine hydrochloride. The method for detecting the content of chloride ions in cyclobenzaprine hydrochloride comprises the following steps:

(1) preparing a test sample: mixing cyclobenzaprine hydrochloride, nitric acid, a non-ionic surfactant and water to obtain a sample solution;

(2) potentiometric titration analysis: and titrating the test sample solution by using a silver nitrate solution, and calculating to obtain the content of chloride ions.

In the invention, by adding the nonionic surfactant, the dissolution of the test sample can be accelerated, the interference of the precipitate adhered to the electrode to the measurement in the titration process is greatly eliminated, and the chloride ions in the cyclobenzaprine hydrochloride can be rapidly and effectively measured. Therefore, the detection method has the characteristics of high accuracy, quick analysis, strong anti-interference performance and high sensitivity.

Wherein the volume V of silver nitrate consumed by titration needs to be recorded_AgNO3(ii) a And calculating the mass of the chloride ions in the test sample solution according to the following formula:

W_Cl ^-＝C_AgNO3×V_AgNO3×35.45；

wherein, C_AgNO3Represents the concentration (mol/L) of silver nitrate, V_AgNO3Represents the volume of silver nitrate consumed by titration (mL), W_Cl ^-Represents the mass (mg) of chloride ions in the test sample solution.

Then the percentage content (% w/w Cl) of the chloride ions in the cyclobenzaprine hydrochloride is obtained by the following formula conversion^-)：

％w/w Cl^-＝W_Cl ^-×100/W_{Sample (I)}；

Wherein, W_{Sample (I)}Represents the mass (mg) of ciclopirox hydrochloride in the test sample solution.

Preferably, in the step (1), the test sample solution comprises the following components in percentage by mass: 0.05-0.3% of cyclobenzaprine hydrochloride, 0.5-3% of nitric acid, 0.05-5% of nonionic surfactant and 90-99% of water.

The content of cyclobenzaprine hydrochloride may be 0.05 to 0.3%, for example, 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, or the like, based on 100% by mass of the test sample solution.

The content of the nitric acid is 0.5 to 3%, for example, 0.5%, 0.6%, 0.8%, 1%, 1.5%, 2%, 2.5%, 3%, or the like, based on 100% by mass of the sample solution.

The content of the nonionic surfactant is 0.05 to 5%, and may be, for example, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, or the like, based on 100% by mass of the sample solution.

The water content may be 90 to 99%, for example, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or the like, based on 100% by mass of the sample solution.

Preferably, in the step (1), the non-ionic surfactant comprises any one or a combination of at least two of triton X-100, polyethylene glycol or polyvinylpyrrolidone, and is preferably triton X-100.

Preferably, in step (1), the concentration of the nitric acid is 14.4-15.2mol/L, and may be, for example, 14.4mol/L, 14.5mol/L, 14.6mol/L, 14.7mol/L, 14.8mol/L, 14.9mol/L, 15.0mol/L, 15.1mol/L, 15.2mol/L, or the like.

The nitric acid is defined herein in terms of its concentration, which is the concentration of nitric acid used, i.e., the concentration of 0.5-3% nitric acid added per se, and not in the test sample solution, i.e., 14.4-15.2mol/L of pure HNO in the test sample solution of the present invention, i.e., 0.5-3% of nitric acid added per se, as distinguished from dilute nitric acid₃。

Preferably, in step (1), the specific steps of preparing the test sample are as follows: firstly, cyclobenzaprine hydrochloride is mixed with water, then nitric acid and nonionic surfactant are added, and stirring is carried out, so as to obtain the sample solution.

Preferably, in the step (2), the concentration of the silver nitrate solution is 0.05-0.2mol/L, for example, 0.05mol/L, 0.06mol/L, 0.08mol/L, 0.1mol/L, 0.12mol/L, 0.14mol/L, 0.16mol/L, 0.18mol/L, 0.2mol/L, etc., preferably 0.1 mol/L.

Preferably, in the step (2), the electrode used for titration is a composite silver-plated platinum ring electrode.

Preferably, the model of the composite silver-plated platinum ring electrode is DMi 141-SC.

Preferably, in the step (2), the titration is performed by using a Mettler potentiometric titrator T50.

Preferably, in the step (2), the reference electrolyte for titration is a potassium nitrate solution.

Preferably, the concentration of the potassium nitrate solution is 0.5 to 2mol/L, and may be, for example, 0.5mol/L, 0.6mol/L, 0.8mol/L, 1mol/L, 1.2mol/L, 1.4mol/L, 1.6mol/L, 1.8mol/L, 2mol/L, or the like, preferably 1 mol/L.

Preferably, the titration is performed under stirring, the rotation speed of the stirring being 20-50%, for example 20%, 25%, 30%, 35%, 40%, 45%, 50% and the like.

Preferably, in step (2), the endpoint detection threshold for titration is 80 to 150mV/mL, and may be, for example, 80mV/mL, 85mV/mL, 90mV/mL, 95mV/mL, 100mV/mL, 110mV/mL, 120mV/mL, 130mV/mL, 140mV/mL, 150mV/mL, or the like, and is preferably 100 mV/mL.

Preferably, the method for detecting the content of chloride ions in cyclobenzaprine hydrochloride comprises the following steps:

(1) preparing a test sample: firstly, mixing cyclobenzaprine hydrochloride with water, then adding nitric acid and a nonionic surfactant, and stirring to obtain a sample solution to be tested;

the test sample solution comprises the following components in percentage by mass: 0.05-0.3% of cyclobenzaprine hydrochloride, 1-3% of nitric acid, 0.05-5% of nonionic surfactant and 90-99% of water;

(2) potentiometric titration analysis: titrating the sample solution to be tested by using 0.05-0.2mol/L silver nitrate solution, and calculating to obtain the content of chloride ions;

wherein the electrode is a composite silver ring intelligent electrode DMi141-SC, the reference electrolyte is 0.5-2mol/L potassium nitrate solution, the stirring rotating speed is 20-50%, and the endpoint recognition threshold value is 50-150 mV/mL.

In addition, in the invention, the method of titrating the sodium chloride standard solution by using the silver nitrate solution is adopted, the repeatability, specificity, linearity, recovery rate and the like of the test method are examined, and the specific titration method is the same as the detection method of the content of the chloride ions in the cyclobenzaprine hydrochloride.

Compared with the prior art, the invention has the following beneficial effects:

the nonionic surfactant is added in the method, so that the dissolution of a test sample can be accelerated, the interference of precipitates adhered to an electrode to the measurement in the titration process is greatly eliminated, and the chloride ions in the cyclobenzaprine hydrochloride can be rapidly and effectively measured.

Detailed Description

The technical solution of the present invention is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.

The following examples used test equipment as follows:

potentiometric titrators: mettler potentiometric titrator T50; an electrode: a composite silver ring intelligent electrode DMi 141-SC; electromagnetic stirrer: a stir bar covered with polyethylene.

The following examples employ the following sources of components:

cyclobenzaprine hydrochloride (manufacturer: Medicihem, lot: A-190305)&A-190306); triton X-100 (manufacturer: SIGMA-ALDRICH, viscosity: 243-291 cps); polyethylene glycol 400 (manufacturer: DOW, molecular weight: 396); polyvinylpyrrolidone (manufacturer: JRS, molecular weight: 3.8X 10)⁴) (ii) a Nitric acid (manufacturer: national chemical reagent limited, concentration: 65.0-68.0 wt%); silver nitrate (manufacturer: Shanghai city, Measure technique research institute, concentration: 0.1006 mol/L).

Example 1

The embodiment provides a method for detecting the content of chloride ions in cyclobenzaprine hydrochloride, which specifically comprises the following steps:

(1) preparing a test sample: transferring about 200mg of cyclobenzaprine hydrochloride batch 1 to a suitable beaker, adding 200mL of water to the beaker, stirring with a stirring magneton until dissolved, adding 5mL of nitric acid and 4mL of Triton X-100 solution (5 wt%) to obtain the test sample solution;

(2) potentiometric titration analysis: titrating the sample solution to be tested by using 0.1mol/L silver nitrate solution, and calculating to obtain the content of chloride ions;

the electrode is a composite silver ring intelligent electrode DMi141-SC, the reference electrolyte is 1mol/L potassium nitrate solution, the stirring speed is 30%, and the endpoint recognition threshold value is 100 mV/mL.

Example 2

The embodiment provides a method for detecting the content of chloride ions in cyclobenzaprine hydrochloride, which specifically comprises the following steps:

(1) preparing a test sample: transferring about 200mg of cyclobenzaprine hydrochloride batch 2 to a suitable beaker, adding 200mL of water to the beaker, stirring with a stirring magneton until dissolved, adding 6mL of nitric acid and 3mL of Triton X-100 solution (5 wt%) to obtain the test sample solution;

(2) potentiometric titration analysis: titrating the sample solution to be tested by using 0.1mol/L silver nitrate solution, and calculating to obtain the content of chloride ions;

the electrode is a composite silver ring intelligent electrode DMi141-SC, the reference electrolyte is 1mol/L potassium nitrate solution, the stirring speed is 40%, and the endpoint recognition threshold value is 100 mV/mL.

Example 3

The embodiment provides a method for detecting the content of chloride ions in cyclobenzaprine hydrochloride, which specifically comprises the following steps:

(1) preparing a test sample: transferring a batch of cyclobenzaprine hydrochloride of about 200mg to a suitable beaker, adding 200mL of water to the beaker, stirring with a stirring magneton until dissolved, adding 5mL of nitric acid and 4mL of polyethylene glycol to obtain the test sample solution;

(2) potentiometric titration analysis: titrating the sample solution to be tested by using 0.1mol/L silver nitrate solution, and calculating to obtain the content of chloride ions;

the electrode is a composite silver ring intelligent electrode DMi141-SC, the reference electrolyte is 1mol/L potassium nitrate solution, the stirring speed is 40%, and the endpoint recognition threshold value is 100 mV/mL.

Example 4

The embodiment provides a method for detecting the content of chloride ions in cyclobenzaprine hydrochloride, which specifically comprises the following steps:

(1) preparing a test sample: transferring a batch of cyclobenzaprine hydrochloride of about 200mg to a suitable beaker, adding 200mL of water to the beaker, stirring with a stirring magnet until dissolved, adding 5mL of nitric acid and 4mL of polyvinylpyrrolidone solution (5 wt%), to give the test sample solution;

(2) potentiometric titration analysis: titrating the sample solution to be tested by using 0.1mol/L silver nitrate solution, and calculating to obtain the content of chloride ions;

the electrode is a composite silver ring intelligent electrode DMi141-SC, the reference electrolyte is 1mol/L potassium nitrate solution, the stirring speed is 40%, and the endpoint recognition threshold value is 100 mV/mL.

Example 5

The embodiment provides a method for detecting the content of chloride ions in cyclobenzaprine hydrochloride, which specifically comprises the following steps:

(1) preparing a test sample: transferring about 200mg batch 1 of cyclobenzaprine hydrochloride into a suitable beaker, adding 200mL of water to the beaker, stirring with a stirring magneton until dissolved, adding 5mL of nitric acid and 1mL of Triton X-100 solution (5 wt%) to give the test sample solution;

(2) potentiometric titration analysis: titrating the sample solution to be tested by using 0.1mol/L silver nitrate solution, and calculating to obtain the content of chloride ions;

the electrode is a composite silver ring intelligent electrode DMi141-SC, the reference electrolyte is 1mol/L potassium nitrate solution, the stirring speed is 30%, and the endpoint recognition threshold value is 100 mV/mL.

Example 6

The embodiment provides a method for detecting the content of chloride ions in cyclobenzaprine hydrochloride, which specifically comprises the following steps:

(1) preparing a test sample: transferring about 200mg of cyclobenzaprine hydrochloride batch 1 to a suitable beaker, adding 200mL of water to the beaker, stirring with a stirring magneton until dissolved, adding 5mL of nitric acid and 10mL of Triton X-100 solution (5 wt%) to obtain the test sample solution;

(2) potentiometric titration analysis: titrating the sample solution to be tested by using 0.1mol/L silver nitrate solution, and calculating to obtain the content of chloride ions;

the electrode is a composite silver ring intelligent electrode DMi141-SC, the reference electrolyte is 1mol/L potassium nitrate solution, the stirring speed is 30%, and the endpoint recognition threshold value is 100 mV/mL.

Example 7

The embodiment provides a method for detecting the content of chloride ions in cyclobenzaprine hydrochloride, which specifically comprises the following steps:

(1) preparing a test sample: transferring about 200mg of cyclobenzaprine hydrochloride batch 1 to a suitable beaker, adding 200mL of water to the beaker, stirring with a stirring magneton until dissolved, adding 5mL of nitric acid and 4mL of Triton X-100 solution (5 wt%) to obtain the test sample solution;

(2) potentiometric titration analysis: titrating the sample solution to be tested by using 0.1mol/L silver nitrate solution, and calculating to obtain the content of chloride ions;

the method comprises the following steps of taking a silver electrode as an indicating electrode, taking a double-salt bridge type saturated calomel electrode as a reference electrode, adding a 3mol/L potassium chloride solution into a first salt bridge of the double-salt bridge type saturated calomel electrode, adding a 0.1mol/L potassium nitrate solution into a second salt bridge of the double-salt bridge type saturated calomel electrode, stirring at a rotating speed of 30%, and setting an endpoint recognition threshold value to be 100 mV/mL.

Comparative example 1

The comparative example provides a method for detecting the content of chloride ions in cyclobenzaprine hydrochloride, which specifically comprises the following steps:

(1) preparing a test sample: transferring a batch of cyclobenzaprine hydrochloride of about 200mg to a suitable beaker, adding 200mL of water to the beaker, stirring with a stirring magneton until dissolved, adding 5mL of nitric acid to obtain the test sample solution;

(2) potentiometric titration analysis: titrating the test sample solution by using 0.1mol/L silver nitrate solution;

the electrode is a composite silver ring intelligent electrode DMi141-SC, the reference electrolyte is 1mol/L potassium nitrate solution, the stirring speed is 30%, and the endpoint recognition threshold value is 100 mV/mL. (ii) a

As a result, it was found that: the titration endpoint could not be reached.

Comparative example 2

The comparative example provides a method for detecting the content of chloride ions in cyclobenzaprine hydrochloride, which specifically comprises the following steps:

(1) preparing a test sample: transferring about 200mg of cyclobenzaprine hydrochloride batch 1 to a suitable beaker, adding 200mL of water to the beaker, stirring with a stirring magneton until dissolved, adding 5mL of nitric acid and 4mL of sodium dodecylbenzenesulfonate (5 wt%) to give the test sample solution;

(2) potentiometric titration analysis: titrating the test sample solution by using 0.1mol/L silver nitrate solution;

the electrode is a composite silver ring intelligent electrode DMi141-SC, the reference electrolyte is 1mol/L potassium nitrate solution, the stirring speed is 30%, and the endpoint recognition threshold value is 100 mV/mL.

As a result, it was found that: the titration endpoint could not be reached.

Comparative example 3

The comparative example provides a method for detecting the content of chloride ions in cyclobenzaprine hydrochloride, which specifically comprises the following steps:

(1) preparing the microemulsion: the optimal proportion of the preparation table is surface active mixed liquid of deionized water, Triton X-100, cyclohexane and n-butyl alcohol in a volume ratio of 3:4:4: 2;

(2) preparing a silver nitrate solution: accurately weighing dried silver nitrate solid 169.87mg, fully dissolving with deionized water, metering the volume in a 100mL volumetric flask, preparing a standard 0.01mol/L silver nitrate reagent, and filling the reagent in a brown flask to be placed in a dark place;

(3) preparation of nitric acid diluent: adding 50mL of analytically pure nitric acid into 50mL of water to obtain a diluent, wherein the mass fraction of the analytically pure nitric acid is 65%.

(4) Preparing a stable silver chloride suspension: absorbing a certain volume of chloride ion standard solution into a brown colorimetric tube, then adding 2mL of the nitric acid solution prepared in the step (3), 2mL of the microemulsion prepared in the step (1) and 2mL of the silver nitrate solution prepared in the step (2) into the colorimetric tube, adding deionized water to a calibration scale mark, shaking up, standing in a dark place for 15min, absorbing a proper amount of silver chloride suspension generated by reaction by using a disposable plastic dropper, and transferring the silver chloride suspension into a cuvette with the diameter of 10 mm;

(5) determination of detection wavelength

And (4) taking a proper amount of 1mg/L chloride ion standard solution, preparing a stable silver chloride suspension according to the step (4), and collecting a spectral absorption curve of the suspension in the range of 360-900 nm by using a spectrometer.

(6) And (3) drawing a standard curve graph of chloride ion content and absorbance: taking 7 25mL brown colorimetric tubes, respectively attaching labels of 0mg/L, 1mg/L and 2mg/L … … 6mg/L to the brown colorimetric tubes, sequentially adding chloride ion standard solutions with the volumes of 0mL, 1mg/L, 2mg/L, 3, 4, 5 and 6mL, sequentially adding 4mL of nitric acid diluent prepared in the step (3), 2mL of microemulsion prepared in the step (1) and 2mL of silver nitrate solution prepared in the step (2) according to an experimental method, fixing the volume to a brown tube scale line by using deionized water, uniformly oscillating, placing in a dark place for 15min, collecting the absorbance of the solution at 420nm after reaction in each colorimetric tube by using a spectrometer, and establishing a quantitative model between the chloride ion content and the absorbance;

(7) preparation and testing of test sample solutions: accurately weighing 4mg of cyclopropionaline hydrochloride, fully dissolving the cyclopropionaline hydrochloride with deionized water, then placing the cyclopropione hydrochloride into a 200mL volumetric flask, and sequentially adding 4mL of nitric acid diluent prepared in the step (3), 2mL of microemulsion prepared in the step (1) and 2mL of silver nitrate solution prepared in the step (2) according to an experimental method.

As a result, it was found that: the sample solution can not form a stable suspension, the absorbance is reduced along with the time, and the content of the chloride ions can not be measured by a spectrophotometry method.

Methodology investigation

The methodology investigation of the detection methods for the content of chloride ions in the ciclopirox hydrochloride provided in the above examples 1 to 7 was carried out, and the specific test methods are as follows:

(1) preparing a reference substance solution: precisely weighing 770mg of sodium chloride into a measuring flask of 200mL, and dissolving with water to fix the volume to a scale. The solution was used as a control stock solution. The control stock solution was weighed into a measuring flask of 10mL to 200mL, diluted to the mark with water, and shaken up. The solution in the measuring flask is completely transferred to a suitable beaker and 3-8mL of nitric acid and 2-6mL of Triton X-100 solution (5%) are added and stirred well as a control solution for analysis.

(2) The test method comprises the following steps:

sample introduction reproducibility: continuously analyzing 3 parts of the reference substance solution, and calculating the recovery rate of chloride ions in the sodium chloride solution;

the specificity is as follows: testing whether the blank solution (except for not containing cyclobenzaprine hydrochloride, the concentrations of other components and all components are completely consistent with the components of the test sample in corresponding examples 1-7) responds to chloride ions; wherein, the NO represents that the chlorine ions in the blank solution have NO obvious response, and the YES represents that the chlorine ions in the blank solution have obvious response;

linearity: seven chloride ion masses (example 1: 9.976-29.929 mg; example 2: 9.594-28.782 mg; example 3: 10.091-30.272 mg; example 4: 9.646-28.938 mg; example 5: 10.118-30.354 mg; example 6: 9.516-28.548 mg; example 7: 9.755-29.265mg) were examined for the consumption of the silver nitrate solution, each consumption being fitted to the corresponding chloride ion mass to a linear equation;

and (3) recovery rate: the recovery at three concentration levels (50mg/mL, 100mg/mL, 150mg/mL) was examined;

repeatability: 6 parts of test sample solutions adopted in corresponding examples are prepared in parallel, and RSD of the chloride ion determination result is calculated;

intermediate precision: preparing six samples on different balance rows by a second tester, and calculating the RSD of the chloride ion determination result;

durability: three samples with the sample amount of 150mg and 250mg are prepared in parallel, and the difference value of the chloride ion determination result and the repeatability result is obtained.

The specific test results are shown in table 1 below:

TABLE 1

As can be seen from the test data in table 1, the sample injection reproducibility is: and continuously analyzing 3 parts of the reference substance solution, and calculating the recovery rate of chloride ions in the sodium chloride solution, wherein the recovery rate is 95.0-105.0% and the% RSD is less than 2.5, which shows that the detection method has excellent repeatability.

The specificity is as follows: analysis and test of a blank solution (except that the test solution does not contain cyclobenzaprine hydrochloride, the concentrations of other components and the concentrations of the components are completely consistent with those of the test sample components in corresponding examples 1-7) show that the blank solvents adopted in the examples have no chloride ion response, and the specificity of the detection method is excellent.

Linearity: the consumption of the silver nitrate solution under seven concentration levels is considered, and the correlation coefficients are all above 0.999, which shows that the detection method of the invention has excellent linearity.

And (3) recovery rate: recovery was examined at three concentration levels (50-150mg/mL) and resulted in a range of 95.0% -105.0% with% RSD less than 2.5.

Repeatability: in parallel, 6 samples were prepared and the% RSD of the chloride ion assay was less than 3.0.

Intermediate precision: the second tester prepared six samples on different balance rows, the% RSD of the chloride ion determination result was less than 5.0, and the chloride ion content differed by no more than 0.3% from the reproducibility result.

Durability: three samples with the sample amount of 150mg and 250mg are prepared in parallel, and the difference of the chloride ion determination result and the repeatability result is not more than 0.3%.

In conclusion, in the invention, the non-ionic surfactant is added, so that the dissolution of the test sample can be accelerated, the interference of the precipitate adhered to the electrode in the titration process to the measurement is greatly eliminated, and the chloride ions in the cyclobenzaprine hydrochloride can be rapidly and effectively measured. Therefore, the detection method has the characteristics of high accuracy, quick analysis, strong anti-interference performance and high sensitivity.

The applicant states that the method for detecting the content of chloride ions in ciclopirox hydrochloride of the present invention is illustrated by the above examples, but the present invention is not limited to the above examples, i.e. the present invention is not limited to the above examples. It should be understood by those skilled in the art that any modification of the present invention, equivalent substitutions of the raw materials of the product of the present invention, addition of auxiliary components, selection of specific modes, etc., are within the scope and disclosure of the present invention.