A method for detecting genotoxic impurity piperonyl chloride in dopamine hydrochloride and a quality control method for dopamine hydrochloride

Abstract

The present invention proposes a method for detecting piperonyl chloride in dopamine hydrochloride and a method for quality control of dopamine hydrochloride. The detection method comprises: using a gas chromatography-mass spectrometer to detect a dopamine hydrochloride sample to be detected; wherein the detection is performed by split injection, constant flow of carrier gas and programmed temperature rise. The detection method of the present invention can effectively separate and detect piperonyl chloride, has the advantages of high accuracy, good separation, low detection limit, good applicability, durability and specificity, simple and fast operation, high efficiency, etc., and is suitable for wide application.

Description

Technical Field

[0001] The present invention relates to the field of medicine, and in particular to a method for detecting piperonyl chloride in dopamine hydrochloride. Background Art

[0002] Dopamine is a precursor of norepinephrine biosynthesis and one of the central neurotransmitters. It has the function of stimulating β-receptors, α-receptors and dopamine receptors. Stimulating cardiac β-receptors can increase myocardial contractility and cardiac output. Stimulating dopamine receptors and α-receptors can dilate the kidneys, mesentery, coronary arteries and cerebral blood vessels, increase blood flow, and have a mild contraction effect on peripheral blood vessels, increase arterial blood pressure, increase renal blood flow, increase glomerular filtration rate, thereby promoting increased urine volume and urinary sodium excretion. It is clinically used for various types of shock, especially for those with shock accompanied by weakened cardiac contractility and renal insufficiency.

[0003] At present, the mainstream preparation process of dopamine hydrochloride is as follows:

[0004]

[0005] This method uses piperonyl ethylamine as the starting material, and obtains dopamine hydrochloride through a one-step ring-opening reaction under the action of hydrochloric acid and phenol. The route is short, but the synthesis process can produce trace amounts of piperonyl chloride. Piperonyl chloride is a halogenated alkane and a genotoxic impurity. According to the ICH M7 guidelines, the content of piperonyl chloride must be strictly controlled. Genotoxic impurities directly or indirectly damage cell DNA, produce gene mutations or in vivo mutagenesis, and have the potential or tendency to cause cancer. In recent years, genotoxic impurities have gradually attracted widespread attention due to their significant safety risks. Regulatory agencies around the world, such as ICH, FDA, and EMA, have more specific requirements for genotoxic impurities. More and more pharmaceutical companies are focusing on the control and detection of genotoxic impurities in the process of new drug research and development. Therefore, the detection method of the genotoxic impurity piperonyl chloride in dopamine hydrochloride is urgently needed.

[0006] Summary of the invention

[0007] The present invention aims to solve at least one of the technical problems existing in the prior art to a certain extent. To this end, the present invention provides a method for detecting piperonyl chloride in dopamine hydrochloride and a quality control method for dopamine hydrochloride, by which piperonyl chloride can be effectively separated and detected, and the method has the advantages of high accuracy, good separation, low detection limit, good applicability, durability and specificity, simple and fast operation, high efficiency, etc., and is suitable for wide application.

[0008] In one aspect of the present invention, the present invention provides a method for detecting piperonyl chloride in dopamine hydrochloride. According to an embodiment of the present invention, the method comprises: using a gas chromatograph-mass spectrometer to detect the dopamine hydrochloride sample to be detected; wherein the detection is performed by split injection, constant flow of carrier gas and programmed temperature.

[0009] When the inventors used a gas chromatograph-mass spectrometer to detect piperonyl chloride in dopamine hydrochloride, they found that the sample injection method, carrier flow rate and heating method would significantly affect the detection effect. When a split injection method, a constant carrier gas flow rate and a programmed temperature increase method were used, it was helpful to separate piperonyl chloride from dopamine hydrochloride, and problems such as tailing or fronting were not likely to occur. The method has the advantages of high accuracy, good separation, low detection limit, good applicability, durability and specificity, simple and fast operation, high efficiency, etc., and is suitable for wide application.

[0010] According to an embodiment of the present invention, the above-mentioned method for detecting piperonyl chloride in dopamine hydrochloride may also have the following additional technical features:

[0011] According to an embodiment of the present invention, the split ratio used in the split injection is 1: 1 to 15: 1, preferably 3: 1 to 7: 1. The inventors found that the split ratio would affect the peak intensity of the target peak, and obtained the above-mentioned preferred split ratio through a large number of experimental screenings, thereby avoiding chromatographic column overload or too low response value.

[0012] According to an embodiment of the present invention, the flow rate of the carrier gas is 0.5 to 5 ml / min, preferably 0.8 to 1.4 ml / min. The inventors found that the flow rate of the carrier gas will affect the separation effect. If the flow rate is too fast, the separation efficiency will be reduced. If the flow rate is too slow, the chromatographic peak is prone to tailing or fronting. Furthermore, the inventors obtained the above-mentioned preferred carrier gas flow rate through a large number of experiments, thereby achieving a good separation effect.

[0013] According to an embodiment of the present invention, the programmed temperature rise method is as follows: the starting temperature is 70-90°C, maintained for 1-3 minutes, then raised to 180-200°C at a rate of 25-40°C / min, and maintained for 1-1.8 minutes, then raised to 280-320°C at a rate of 25-40°C / min, and maintained for 0.5-2 minutes. The inventors obtained the above-mentioned preferred programmed temperature rise method through a large number of experiments, thereby achieving a good separation effect.

[0014] According to an embodiment of the present invention, the detection adopts an ion scanning mode, with m / z of 51, 77, and 135 and a residence time of 0.08, 0.08, and 0.08, so as to accurately identify piperonyl chloride.

[0015] According to an embodiment of the present invention, the injection port temperature used in the detection is 260-300° C., the transmission line temperature is 280-320° C., and the ion source temperature is 280-320° C. Thus, the piperonyl chloride can be completely gasified to avoid contamination of the ion source.

[0016] According to an embodiment of the present invention, the chromatographic column used for the detection is Agilent DB-35MS, the injection volume is 1 μl, the carrier gas is helium, the split ratio is 5:1, the injection port temperature is 280°C, the transmission line temperature is 300°C, the ion source temperature is 300°C, the flow rate is 1.0 ml / min, the solvent delay is 2.50 min, the scanning mode is ion scanning mode, m / z is 51, 77, 135, the residence time is 0.08, 0.08, 0.08, and the programmed temperature rise method is: the starting temperature is 80°C, maintained for 2 min, then increased to 190°C at a rate of 30°C / min, and maintained for 1.5 min, then increased to 300°C at a rate of 30°C / min, and maintained for 1 min.

[0017] The inventors obtained the above-mentioned optimal detection conditions after a large number of experiments, which have the advantages of high accuracy, good separation, low detection limit, good applicability, durability and specificity, simple and fast operation, high efficiency, etc., and are suitable for large-scale application.

[0018] In another aspect of the present invention, the present invention proposes a dopamine hydrochloride quality control method. According to an embodiment of the present invention, the method comprises: using the aforementioned method to test the dopamine hydrochloride sample to be tested, and determining the test result; based on the test result, determining whether the quality of the dopamine hydrochloride sample to be tested meets the standard. Therefore, the method according to the embodiment of the present invention can accurately determine whether the quality of dopamine hydrochloride meets the requirements, thereby effectively controlling the quality.

[0019] The present invention does not strictly limit the method for determining whether the quality of dopamine hydrochloride meets the standard based on the test results, and can be flexibly selected according to actual conditions. For example, the detected content of piperonyl chloride or dopamine hydrochloride can be compared with a preset threshold value. When the content of dopamine hydrochloride is higher than the threshold value and / or the content of piperonyl chloride is lower than the threshold value, it is determined that the quality meets the standard. The present invention requires that the limit of piperonyl chloride should not exceed 1500ng / g (1.5ppm).

[0020] Those skilled in the art will appreciate that the features and advantages described above for the method for detecting piperonyl chloride in dopamine hydrochloride are also applicable to the quality control method for dopamine hydrochloride, and will not be described in detail here.

[0021] Additional aspects and advantages of the present invention will be given in part in the following description and in part will be obvious from the following description, or will be learned through practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The above and / or additional aspects and advantages of the present invention will become apparent and easily understood from the description of the embodiments in conjunction with the following drawings, in which:

[0023] Figure 1 Shows the blank solution chromatogram in Example 2 of the present invention;

[0024] Figure 2 Shows a chromatogram of the reference solution in Example 2 of the present invention;

[0025] Figure 3 The chromatogram of the test solution in Example 2 of the present invention is shown;

[0026] Figure 4 shows a chromatogram of a 100% spiked test solution in Example 2 of the present invention;

[0027] Figure 5 A linear graph in Example 2 according to the present invention is shown. DETAILED DESCRIPTION

[0028] The scheme of the present invention will be explained below in conjunction with the embodiments. It will be appreciated by those skilled in the art that the following embodiments are only used to illustrate the present invention and should not be considered as limiting the scope of the present invention. Where specific techniques or conditions are not indicated in the embodiments, the techniques or conditions described in the literature in this area or the product specifications are used. The reagents or instruments used are not indicated by the manufacturer and are all conventional products that can be obtained commercially.

[0029] Example 1

[0030] In this embodiment, the content of piperonyl chloride in the dopamine hydrochloride solution was detected according to the following method:

[0031] 1. Solution preparation

[0032] Preparation of reference solution: Take an appropriate amount of piperonyl chloride reference, weigh it accurately, place it in a volumetric flask, dissolve it with n-hexane and dilute it to the scale, shake well, and make a solution containing about 0.090 μg of piperonyl chloride per 1 ml.

[0033] Preparation of test solution: Take about 0.12g of the test sample (dopamine hydrochloride raw material), accurately weigh it, put it in a 5ml centrifuge tube, accurately add 1ml of first-grade water to completely dissolve it, add 2ml of n-hexane, vortex for 30s, take the n-hexane layer and filter it through a 0.22μm nylon filter membrane, and test it on the machine.

[0034] 2. Detection

[0035] Accurately pipette 1 μl of the reference solution and the test solution respectively, inject into the gas chromatography-mass spectrometer, and measure the peak area according to the external standard method. The specific detection conditions are as follows:

[0036] Table 1 GC-MS detection parameters

[0037]

[0038] Example 2

[0039] In this embodiment, the content of piperonyl chloride in the dopamine hydrochloride solution was detected according to the following method:

[0040] 1. Solution preparation

[0041] Preparation of reference solution: Take an appropriate amount of piperonyl chloride reference, weigh it accurately, place it in a volumetric flask, dissolve it with n-hexane and dilute it to the scale, shake well, and make a solution containing about 0.090 μg of piperonyl chloride per 1 ml.

[0042] Preparation of test solution: Take about 0.12g of the test sample (dopamine hydrochloride raw material), accurately weigh it, put it in a 5ml centrifuge tube, accurately add 1ml of first-grade water to completely dissolve it, add 2ml of n-hexane, vortex for 30s, take the n-hexane layer and filter it through a 0.22μm nylon filter membrane, and test it on the machine.

[0043] 2. Detection

[0044] Accurately pipette 1 μl of the reference solution and the test solution respectively, inject into the gas chromatography-mass spectrometer, and measure the peak area according to the external standard method. The specific detection conditions are as follows:

[0045] Table 2 GC-MS detection parameters

[0046]

[0047] Example 3

[0048] In this embodiment, the content of piperonyl chloride in the dopamine hydrochloride solution was detected according to the following method:

[0049] 1. Solution preparation

[0050] Preparation of reference solution: Take an appropriate amount of piperonyl chloride reference, weigh it accurately, place it in a volumetric flask, dissolve it with n-hexane and dilute it to the scale, shake well, and make a solution containing about 0.090 μg of piperonyl chloride per 1 ml.

[0051] Preparation of test solution: Take about 0.12g of the test sample (dopamine hydrochloride raw material), accurately weigh it, put it in a 5ml centrifuge tube, accurately add 1ml of first-grade water to completely dissolve it, add 2ml of n-hexane, vortex for 30s, take the n-hexane layer and filter it through a 0.22μm nylon filter membrane, and test it on the machine.

[0052] 2. Detection

[0053] Accurately pipette 1 μl of the reference solution and the test solution respectively, inject into the gas chromatography-mass spectrometer, and measure the peak area according to the external standard method. The specific detection conditions are as follows:

[0054] Table 3 GC-MS detection parameters

[0055]

[0056] Example 4

[0057] In this example, the detection method of Example 1 was methodologically verified:

[0058] 1. Solution preparation:

[0059] (1) Preparation of reference solution

[0060] Piperonyl chloride reference stock solution 1 (concentration: 4523 μg / ml): Take an appropriate amount of piperonyl chloride standard, accurately weigh 0.02262 g and place it in a 5 ml volumetric flask, add methanol to dissolve, dilute to the scale with methanol, shake well, and you have it.

[0061] Intermediate solution 1 (concentration: 104.029 μg / ml): Accurately measure 23 μl of piperonyl chloride reference stock solution 1, place it in a 1 ml volumetric flask, add n-hexane to dilute to the scale, shake well, and obtain.

[0062] Intermediate solution 2 (concentration: 10.403 μg / ml): Accurately measure 100 μl of intermediate solution 1, place it in a 1 ml volumetric flask, add n-hexane to dilute to the scale, shake well, and obtain.

[0063] Intermediate solution 3 (concentration: 1.040 μg / ml): Accurately measure 100 μl of intermediate solution 2, place it in a 1 ml volumetric flask, add n-hexane to dilute to the scale, shake well, and obtain.

[0064] Reference solution (concentration: 93.600 ng / ml): Accurately measure 90 μl of intermediate solution 3, place in a 1 ml volumetric flask, add n-hexane to dilute to the scale, shake well, and obtain.

[0065] (2) Preparation of detection limit and quantification limit solutions

[0066] Quantitative limit solution (concentration: 26.000 ng / ml): Accurately measure 25 μl of intermediate solution 3, place it in a 1 ml volumetric flask, add n-hexane to dilute to the scale, shake well, and obtain.

[0067] Detection limit solution (concentration: 13.520 ng / ml): Accurately measure 13 μl of intermediate solution 3, place it in a 1 ml volumetric flask, add n-hexane to dilute to the scale, shake well, and obtain.

[0068] (3) Preparation of linear solution

[0069] Linear solution 1 (concentration: 26.000 ng / ml): Accurately measure 25 μl of intermediate solution 3, place it in a 1 ml volumetric flask, dilute to the scale with n-hexane, shake well, and obtain.

[0070] Linear solution 2 (concentration: 46.800 ng / ml): Accurately measure 45 μl of intermediate solution 3, place it in a 1 ml volumetric flask, dilute to the scale with n-hexane, shake well, and obtain.

[0071] Linear solution 3 (concentration: 93.600 ng / ml): Accurately measure 90 μl of intermediate solution 3, place in a 1 ml volumetric flask, dilute to the scale with n-hexane, shake well, and obtain.

[0072] Linear solution 4 (concentration: 140.440 ng / ml): Accurately measure 27 μl of intermediate solution 2, place in a 2 ml volumetric flask, dilute to the scale with n-hexane, shake well, and obtain.

[0073] Linear solution 5 (concentration: 187.254 ng / ml): Accurately measure 36 μl of intermediate solution 2, place in a 2 ml volumetric flask, dilute to the scale with n-hexane, shake well, and obtain.

[0074] (4) Preparation of test solution and blank solution

[0075] Take about 0.12g of the test sample, weigh it accurately, put it in a 5ml centrifuge tube, accurately add 1ml of first-grade water to completely dissolve it, add 2ml of n-hexane, vortex for 30s, take 1ml of the n-hexane layer and filter it through a 0.22μm nylon filter membrane to obtain the test sample solution. Take n-hexane as the blank solution.

[0076] (5) Preparation of spiked test solution

[0077] Quantitation limit spiked test solution: Take about 0.12g of the test sample, accurately weigh it, place it in a 5ml centrifuge tube, accurately add 50μl of intermediate solution 3, and then accurately add 1ml of first-grade water to completely dissolve it, add 2ml of n-hexane, vortex for 30s, take 1ml of the n-hexane layer and filter it through a 0.22μm nylon filter membrane.

[0078] 50% spiked test sample solution: Take about 0.12g of the test sample, accurately weigh it, put it in a 5ml centrifuge tube, accurately add 9μl of intermediate solution 2, and then accurately add 1ml of first-grade water to completely dissolve it, add 2ml of n-hexane, vortex for 30s, take 1ml of the n-hexane layer and filter it through a 0.22μm nylon filter membrane.

[0079] 100% spiked test sample solution: Take about 0.12g of the test sample, accurately weigh it, place it in a 5ml centrifuge tube, accurately add 18μl of intermediate solution 2, and then accurately add 1ml of first-grade water to completely dissolve it, add 2ml of n-hexane, vortex for 30s, take 1ml of the n-hexane layer and filter it through a 0.22μm nylon filter membrane to obtain.

[0080] 150% spiked test sample solution: Take about 0.12g of the test sample, accurately weigh it, put it in a 5ml centrifuge tube, accurately add 27μl of intermediate solution 2, and then accurately add 1ml of first-grade water to completely dissolve it, add 2ml of n-hexane, vortex for 30s, take 1ml of the n-hexane layer and filter it through a 0.22μm nylon filter membrane.

[0081] (6) Preparation of intermediate precision solution

[0082] Intermediate solution 4 (concentration: 104.029 μg / ml): Accurately measure 23 μl of reference stock solution 1, place it in a 1 ml volumetric flask, add n-hexane to dilute to the scale, shake well, and obtain.

[0083] Intermediate solution 5 (concentration: 10.403 μg / ml): Accurately measure 100 μl of intermediate solution 4, place it in a 1 ml volumetric flask, add n-hexane to dilute to the scale, shake well, and obtain.

[0084] Intermediate solution 6 (concentration: 1.040 μg / ml): Accurately measure 100 μl of intermediate solution 5, place it in a 1 ml volumetric flask, add n-hexane to dilute to the scale, shake well, and obtain.

[0085] Intermediate precision 100% spiked test sample solution: take about 0.12g of the test sample, place it in a 5ml centrifuge tube, accurately add 18μl of intermediate solution 5, then accurately add 1ml of first-grade water to completely dissolve, add 2ml of n-hexane, vortex for 30s, take 1ml of the n-hexane layer and filter it through a 0.22μm nylon filter membrane.

[0086] 2. System Applicability

[0087] The reference solution was injected 6 times continuously, and the results are as follows:

[0088] Table 4 System suitability results

[0089]

[0090] Conclusion: It has been verified that the RSD of the peak area of ​​the reference solution injected six times in a row is less than 10.0%, and the system suitability meets the requirements.

[0091] 3. Exclusivity

[0092] The blank solution, test solution, reference solution 1, and 100% spiked test solution were tested respectively. The test results are shown in the following table and Figure 1-Figure 4shown.

[0093] Table 5 Specificity

[0094]

[0095] Conclusion: It has been verified that the blank solution, test solution, 100% spiked test solution and reference solution have no interference with the target qualifier ions, and the specificity meets the requirements.

[0096] 4. Accuracy

[0097] Three samples of the spiked test solution were tested separately. The results are as follows:

[0098] Table 6 Accuracy results

[0099]

[0100] Note: The sample content is used for calculation, so the non-detected result is recorded as 0; Accuracy 1 is 50% spiked test solution, Accuracy 2 is 100% spiked test solution, Accuracy 3 is 150% spiked test solution.

[0101] Conclusion: It was verified that the recoveries of 9 spiked test solutions were in the range of 70%-125%, with RSD less than 15.0%, and the accuracy met the requirements.

[0102] 5. Precision-Repeatability

[0103] Because the content of the test solution is low, the repeatability is determined by the spike method. Six portions of 100% spiked test solution were tested separately, and the results are as follows:

[0104] Table 7 Repeatability results

[0105]

[0106] Conclusion: It has been verified that the RSD of the content of the spiked test solution is less than 10.0%, and the repeatability meets the requirements.

[0107] 6. Precision - Intermediate Precision

[0108] Another experimenter (experimenter B) prepared various intermediate precision solutions and tested them at different times. The repeatability results were compared with those of the original experimenter (experimenter A). The results are as follows:

[0109] Table 8 Intermediate precision system suitability results (experimenter B)

[0110]

[0111] Table 9 Intermediate precision results (laborator B)

[0112]

[0113]

[0114] Table 10 Intermediate precision recovery results

[0115]

[0116]

[0117] Note: Sample content is used for calculations, so non-detectable results are recorded as 0.

[0118] Table 11 Intermediate precision results (laborator A, B)

[0119]

[0120] Conclusion: It has been verified that the recoveries of 12 spiked test solutions prepared by different test personnel were in the range of 70%-125%, the RSD of the content was less than 15.0%, and the intermediate precision met the requirements.

[0121] 7. Limit of detection and limit of quantification

[0122] The detection limit solution and the quantification limit solution were tested separately.

[0123] Table 12 Results of detection limit and quantification limit

[0124]

[0125] Conclusion: It has been verified that the minimum signal-to-noise ratio of the detection limit is greater than 3, and the detection limit meets the requirements; the minimum signal-to-noise ratio of the quantification limit is greater than 10, the quantification limit is lower than 30% of the limit, and the RSD of the quantification limit repeatability test is less than 10.0%, and the quantification limit meets the requirements.

[0126] 8. Linearity and range

[0127] The linear solutions were tested in sequence, and the test results are shown in the following table and Figure 5 As shown:

[0128] Table 13 Linearity results

[0129]

[0130] Conclusion: It has been verified that within the accuracy verification range, the linear correlation coefficient is greater than 0.990, and the intercept is less than 25.0% of the limit concentration peak area. The linearity and range meet the requirements.

[0131] 9. Durability (solution stability)

[0132] Take the reference solution and 100% spiked test solution and test them at different time points. The results are as follows:

[0133] Table 14 Stability results of reference solution

[0134]

[0135] Table 15 Stability results of 100% spiked test solution

[0136]

[0137]

[0138] Conclusion: It has been verified that the RSD of the peak area of ​​the same reference solution and spiked test solution at different time points is less than 15.0%, and the stability of the solution meets the requirements.

[0139] Summary: It has been verified that the system applicability, specificity, accuracy, precision, detection limit, quantification limit, linear range and durability (solution stability) of this analytical method all meet the requirements, indicating that this analytical method is suitable for the detection of piperonyl chloride in dopamine hydrochloride.

[0140] Test results

[0141]

[0142] <LOQ means the test result is lower than the limit of quantitation (equivalent to the concentration limit of quantitation in the sample)

[0143] Test conclusion: After testing, the piperonyl chloride test results of this batch of samples were less than the quantitative limit.

[0144] Example 5

[0145] In this embodiment, the content of piperonyl chloride in the dopamine hydrochloride solution was detected according to the following method:

[0146] 1. Solution preparation

[0147] Same as Example 1.

[0148] 2. Detection

[0149] Accurately pipette 1 μl of the reference solution and the test solution respectively, inject into the gas chromatography-mass spectrometer, and measure the peak area according to the external standard method. The specific detection conditions are as follows:

[0150] Table 16 GC-MS detection parameters

[0151]

[0152]

[0153] The test results of Example 1 and Example 5 show that different sample injection methods will affect the test results. When the non-divided flow mode is used, the baseline noise interference is serious due to the excessive injection concentration, so the divided flow mode is used for injection.

[0154] The larger the split ratio, the smaller the effect value of the result. When the split ratio is 20:1, the sensitivity is close to the limit value. In order to ensure that the sensitivity of the analytical method meets the requirements, the split ratio is determined to be 5:1 and 10:1, the baseline noise is small, and the sensitivity meets the limit requirements. The split ratio is 5:1, and the effect is the best.

[0155] Example 6

[0156] In this embodiment, the content of piperonyl chloride in the dopamine hydrochloride solution was detected according to the following method:

[0157] 1. Solution preparation

[0158] Same as Example 1.

[0159] 2. Detection

[0160] Accurately pipette 1 μl of the reference solution and the test solution respectively, inject into the gas chromatography-mass spectrometer, and measure the peak area according to the external standard method. The specific detection conditions are as follows:

[0161] Table 17 GC-MS detection parameters

[0162]

[0163]

[0164] The test results of Example 1 and Example 6 show that different carrier gas flow rates affect the main peak separation effect and retention time. When the carrier gas flow rate is 1.0 ml / min and 2.0 ml / min, the main peak separation effect is good and the retention time is appropriate, among which 1.0 ml / min has a better effect. When the carrier gas flow rate is 3.0 ml / min, the peak emerges too fast, the separation effect is not good, and the peak cannot be effectively separated.

[0165] Example 7

[0166] In this comparative example, the content of piperonyl chloride in the dopamine hydrochloride solution was detected according to the method of Example 1, except that the heating program was as follows:

[0167] Table 18 Program temperature rise method

[0168]

[0169] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.

[0170] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations of the present invention. A person skilled in the art may change, modify, replace and vary the above embodiments within the scope of the present invention.

Claims

1. A method for detecting piperonyl chloride in dopamine hydrochloride, characterized in that: include: The dopamine hydrochloride sample to be tested is tested by using a gas chromatography-mass spectrometer; Wherein, the detection is carried out by split flow injection, constant flow of carrier gas and programmed temperature rise; The split ratio used in the split injection is 1:1 to 15:1; The flow rate of the carrier gas is 0.5-2 ml / min; The programmed temperature rise method is as follows: The starting temperature is 70~90℃, maintained for 1~3min, then raised to 180~200℃ at a rate of 25~40℃ / min, maintained for 1~1.8min, then raised to 280~320℃ at a rate of 25~40℃ / min, maintained for 0.5~2min; The chromatographic column used in the detection is Agilent DB-35 MS.

2. The method according to claim 1, characterized in that The split ratio used in the split injection is 3:1-7:

1.

3. The method according to claim 1, characterized in that The injection volume was 1 μl, the carrier gas was helium, the split ratio was 5:1, the inlet temperature was 280°C, the transfer line temperature was 300°C, the ion source temperature was 300°C, the flow rate was 1.0 ml / min, the solvent delay was 2.50 min, the scanning mode was ion scanning mode, m / z was 51, 77, 135, the dwell time was 0.08, 0.08, 0.08, and the programmed temperature rise method was: the starting temperature was 80°C, maintained for 2 min, then increased to 190°C at a rate of 30°C / min, and maintained for 1.5 min, then increased to 300°C at a rate of 30°C / min, and maintained for 1 min.

Images