Method for detecting residual chloroacetamide in piracetam

Abstract

The invention discloses a method for detecting residual chloroacetamide in piracetam. A sample to be detected is detected by adopting gas chromatography-triple quadrupole tandem mass spectrometry (GC-MS / MS); the gas chromatography parameters are as follows: the temperature of a sample inlet is 245-255 DEG C; the heating procedure is as follows: the initial temperature is 45-55 DEG C, the temperature is raised to 275-285 DEG C at the heating rate of 35-45 DEG C / min, the post-operation temperature is 295-305 DEG C, and the post-operation time is 4.5-5.5 minutes; the mass spectrum parameters are as follows: the temperature of an ion source is 225-235 DEG C, the temperature of a quadrupole is 145-155 DEG C, and the temperature of a transmission line is 245-255 DEG C; the sampling mode is MRM, the solvent delay is 1.5-2.5 min, and the post-operation time is 2.00-5.00 min. The method disclosed by the invention is simple to operate and high in detection speed, and has the advantages of high sensitivity, high precision and high repeatability.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological medicine detection, and particularly relates to a detection method of residual chloroacetamide in piracetam. BACKGROUND

[0002] Piracetam (2-oxo-1-pyrrolidine acetamide) is a pyrrolidone, a cyclic derivative of gamma-aminobutyric acid (GABA), which can act on cognitive function and improve cognitive impairment of patients without causing sedation or stimulating effect. A synthesis method of piracetam is shown in Figure 1 Chloroacetamide is a by-product produced in the synthesis process of piracetam raw materials, is a mutagenic impurity with a warning structure, and the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines stipulate that if chloroacetamide is a genotoxic impurity (because its structure contains a chloroacetamide group, it has potential mutagenicity), the limit value needs to follow the “threshold of toxicological concern” (TTC), which is usually 1.5 μg / day (corresponding to a concentration of about 0.001-0.01% in the drug, depending on the daily dose). Piracetam is the main active ingredient in piracetam preparations, and the acceptable limit of genotoxic impurities is generally calculated according to the threshold of toxicological concern (TTC).

[0003]

[0004] The specification of piracetam reference reagent (original drug) indicates that the maximum daily dose of piracetam is 24 g, and according to the most stringent daily intake of 1.5 μg / d, the acceptable limit of genotoxic impurities is 0.0625 ppm. According to the most stringent standard for the implementation of piracetam, 0.0625 ppm is the acceptable limit of potential genotoxic impurities. Therefore, a method with high sensitivity and accurate quantification needs to be established to detect the substance. SUMMARY

[0005] In order to solve the above technical problems, the present application provides a detection method of residual chloroacetamide in piracetam.

[0006] The present application provides a detection method of residual chloroacetamide in piracetam, which adopts gas chromatography-triple quadrupole tandem mass spectrometry GC-MS / MS to detect the sample to be tested;

[0007] The parameters of the gas chromatography are as follows: the injection port temperature is 245-255℃; the temperature rising program is that the initial temperature is 45-55℃, the temperature is raised to 275-285℃ at a temperature rising rate of 35-45℃ / min, and the post-run temperature is 295-305℃, and the post-run time is 4.5-5.5 min;

[0008] The mass spectrometry parameters: ion source temperature is 225-235 DEG C, quadrupole temperature is 145-155 DEG C, and transmission line temperature is 245-255 DEG C; sampling mode: MRM, ion source: EI; solvent delay 1.5-2.5 min, time 2.00-5.00 min.

[0009] The detection method for the residual chloroacetamide in the piracetam adopted by the application is gas chromatography-triple quadrupole tandem mass spectrometry (GC-MS / MS), which uses gas chromatography as the separation system of the chloroacetamide in the piracetam, and mass spectrometry as the detection system of the chloroacetamide.

[0010] The gas chromatography method has strong separation degree for the sample to be detected, and by selecting appropriate chromatographic column, initial column temperature, temperature rising rate, column flow rate and other parameter conditions, the separation effect of the chloroacetamide and other substances can be effectively improved, sufficient ions can be provided for the mass spectrometry test and analysis, the impurities interfering with the mass spectrometry can be preliminarily separated out, the influence of the interfering impurities on the subsequent mass spectrometry is avoided, good peak type parameters are obtained, and thus the accuracy and precision of the detection result can be effectively improved.

[0011] The detection method for the residual chloroacetamide in the piracetam provided by the application has the advantages of low detection limit, high precision, high repeatability and high accuracy by screening and optimizing the related test conditions of the gas chromatography and mass spectrometry in the GC-MS.

[0012] Preferably, the temperature rising program is that the initial temperature is 50 DEG C, the temperature is raised to 280 DEG C at a temperature rising rate of 40 DEG C / min, and then the operating temperature is 300 DEG C, and the post-operation time is 5 min.

[0013] Preferably, the chromatographic column of the gas chromatography condition is HP-1MS UI, 30m*0.25mm*1.0um.

[0014] Preferably, the parameter conditions of the gas chromatography further include: carrier gas flow rate: 1.2-1.8 ml / min; sample injection volume: 0.8-1.2 ul; split mode: split, split ratio is 8-12:1; control mode: constant flow; carrier gas: He.

[0015] Preferably, the parameter conditions of the mass spectrometry are: solvent delay: 2 min; transmission line temperature: 250 DEG C; quadrupole temperature: 150 DEG C; ion source temperature: 230 DEG C.

[0016] Preferably, the scanning parameters of the mass spectrum are: parent ion 93 m / z, daughter ion 44 m / z; CE is 14-15 V, Dwell is 190-210 ms.

[0017] Preferably, the detection limit of the chloroacetamide is 0.00938 ppm; the quantification limit of the chloroacetamide is 0.0188 ppm.

[0018] Preferably, the solution to be detected includes: a control product stock solution, a control product solution, a sensitivity solution and a test product solution.

[0019] Preferably, the preparation method of the piracetam test product solution is: taking 80 mg of piracetam raw material into a 15 ml centrifuge tube, adding 2.0 ml of methanol, ultrasonic dissolving, mixing and obtaining.

[0020] The detection method provided by the present application can effectively detect chloroacetamide in piracetam by using gas-phase-triple quadrupole tandem mass spectrometry. At the same time, the detection method is investigated through system adaptability, specificity, detection limit (LOD), quantification limit (LOQ), linearity and range, accuracy, repeatability, durability, solution stability, intermediate precision, etc. All verification results meet the acceptance criteria. The detection method for chloroacetamide residue in piracetam provided has the advantages of low detection limit, high precision, high repeatability and high accuracy. For example, the detection limit of the chloroacetamide is 0.00938 ppm, and the quantification limit is 0.0188 ppm. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 A schematic diagram of a synthesis method of piracetam of the present application;

[0022] Figure 2 A chromatogram of a blank solution in Example 1;

[0023] Figure 3 A chromatogram of a control product solution in Example 1;

[0024] Figure 4 A chromatogram of a 100% sample spiked solution in Example 1. DETAILED DESCRIPTION

[0025] The present application will be further described in detail below in combination with examples, comparative examples and performance detection tests. These examples should not be understood as limiting the scope of the present application.

[0026] According to the limit requirement of the present application, the limit of chloroacetamide (hereinafter referred to as chloroacetamide) in piracetam should be less than 0.3125 ppm. According to the properties of the raw material and the target, the present application establishes a GC-MS / MS method for detecting the content of chloroacetamide in piracetam, and verifies the method.

[0027] Under the finally selected conditions, the system suitability, specificity, linearity and range, detection limit, quantification limit, accuracy, repeatability and stability of the method are verified to confirm that the method is suitable for determining the content of chloroacetamide in piracetam.

[0028] Example 1

[0029] A method for detecting the residual chloroacetamide in piracetam, comprising the following steps:

[0030] Step 1: Preparation of the test solution, including: reference substance stock solution, reference substance solution, sensitivity solution, test sample solution, the specific preparation method of each solution is as follows:

[0031] (1) Reference substance stock solution: take about 10 mg of chloroacetamide reference substance, accurately weigh, put into a 10 ml volumetric flask, add methanol to dissolve and dilute to the mark, shake well; accurately take 0.5 ml, put into a 100 ml volumetric flask, dilute to the mark with methanol, shake well; accurately take 0.1 ml, put into a 20 ml volumetric flask, continue to dilute to the mark with methanol, shake well, the final concentration is about 25 ng / ml;

[0032] (2) Reference substance solution: accurately take 2.0 ml of the reference substance stock solution, put into a 20 ml volumetric flask, dilute to the mark with methanol, shake well, the concentration is about 2.5 ng / ml;

[0033] (3) Sensitivity solution: accurately take 0.3 ml of the reference substance stock solution, put into a 10 ml volumetric flask, dilute to the mark with methanol, shake well, the concentration is about 0.75 ng / ml;

[0034] (4) Test sample solution: take about 80 mg of piracetam raw material, accurately weigh, put into a 15 ml centrifuge tube, accurately add 2.0 ml of methanol, ultrasonic to dissolve, mix well;

[0035] Step 2: Detecting the test solution in step 1 by GC-MS / MS,

[0036] The detection method and specific parameters are as follows:

[0037] Chromatographic column was HP-1MS UI (30 m x 0.25 mm x 1.0 μm, carrier gas was helium, detector was MS EI (70 eV), injection port temperature was 250 °C, split ratio was 10:1, carrier gas flow rate was 1.5 ml / min, control mode was constant flow, injection volume was 1 μl, temperature program was initial temperature was 50 °C, increased to 280 °C at a rate of 40 °C per minute, then the run temperature was 300 °C, and the run time was 5.00 minutes; MS parameters: ion source temperature was 230 °C, quadrupole temperature was 150 °C, transfer line temperature was 250 °C; sampling mode: MRM, solvent delay was 2.0 minutes, time was 2.00-5.00 minutes, parent ion was 93 m / z, daughter ion was 44 m / z, CE was 15 V, Dwell was 200 ms;

[0038] Step three: the results of the blank solution, sensitivity solution, and reference solution meet the following requirements:

[0039] (1) Blank solution: the system is clean and stable, and there is no interference at the peak position of each component; if there is interference, the peak area of the interference peak should be no greater than the peak area of the main peak in the sensitivity solution;

[0040] (2) Sensitivity solution: the signal-to-noise ratio (S / N) of each component is not less than 10;

[0041] (3) Injection precision: the RSD of the peak area of the analyte in the initial 6 injections of the reference solution is not greater than 15.0%;

[0042] The RSD of the retention time of the analyte in the initial 6 injections of the reference solution is not greater than 1.0%.

[0043] The methodology validation experiments for the detection of residual chloroacetamide in piracetam are as follows:

[0044] 1. System suitability

[0045] Prepare the reference solution at 100% limit and continuously inject it 6 times, use the reference solution at 30% limit as the sensitivity solution, use the solvent as the blank solution, and test on the machine. The system is clean and stable, and there is no obvious interference at the peak position of each target peak. The signal-to-noise ratio of the test results of the sensitivity solution is not less than 10, the RSD of the peak area of the target peak in 6 consecutive injections is not greater than 15.0%, the RSD of the retention time is not greater than 1.0%, and the recovery rate of the inserted reference solution is between 70.0% and 130.0%. The verification results are shown in Table 1 below:

[0046] Table 1 Test results of system suitability

[0047]

[0048]

[0049] 2. Specificity

[0050] The blank solution chromatogram had no interference at the target peak. For details, refer to Figure 2 .

[0051] The analyte in the control solution showed the target peak. For details, refer to Figure 3 , and the retention time (RT) is shown in Table 2.

[0052] The spiked sample solution at the 100% limit had no adjacent peak. For details, refer to Figure 4 , and the resolution is shown in Table 2.

[0053] Table 2 Retention time test results

[0054] Name Blank Interference Retention Time (min) Separation of Adjacent Peaks from Target Peak Chloroacetamide None 3.008 N / A

[0055] 3. Detection limit

[0056] Prepare 1 portion of 15% control solution (the theoretical relative content in the sample is: chloroacetamide 0.00938 ppm) as the LOD solution, inject 3 times, and obtain the test results shown in Table 3. The signal-to-noise ratio S / N is greater than 3.

[0057] Table 3 Detection limit test results

[0058]

[0059] 4. Quantitative limit

[0060] Prepare 1 portion of 30% control solution (the theoretical relative content in the sample is: chloroacetamide 0.0188 ppm) as the LOQ solution, inject 6 times, and obtain the test results. The signal-to-noise ratio is greater than 10. The RSD of the peak area of the target peak in the continuous 6 LOQs is not greater than 30.0%. The verification results are shown in Table 4.

[0061] Table 4 Quantitative limit test results

[0062]

[0063] 5. Linearity and range

[0064] Prepare a series of linear test solutions from the LOQ to the 200% limit concentration (30%, 50%, 100%, 150%, 200%), inject and analyze each portion of the solution once, calculate the equation and the regression coefficient (r), and obtain the regression coefficient (r) ≥ 0.990. Report the Y-axis intercept ratio and the residual sum of squares. The verification results are shown in Table 5.

[0065] Table 5 Linear test results

[0066]

[0067] The range was determined from the data for accuracy and linearity, and the results are shown in Table 6, and the data for accuracy are shown in Table 7.

[0068] Table 6 Range of the method

[0069] Name Range Chloroacetamide 1.25 ng / ml - 3.75 ng / ml

[0070] 6. Accuracy

[0071] Prepare three replicates of spiked sample solutions at the 50%, 100% and 150% limit levels, and prepare two replicates of sample solutions, and analyze each solution once. The average spiked recovery rate at each concentration level is between 70% and 130%, and the RSD of the recovery rates of the nine spiked sample solutions at the 50%, 100% and 150% limit levels is not more than 15.0%. The verification results are shown below:

[0072] Table 7 Results of the accuracy test

[0073]

[0074] 7. Reproducibility

[0075] Prepare six replicates of spiked sample solutions at the 100% limit level, and analyze each solution once. The RSD of the recovery rates of the six 100% spiked sample solutions is not more than 15.0%. The verification results are shown in Table 8 below:

[0076] Table 8 Results of the reproducibility test

[0077]

[0078] 8. Intermediate precision

[0079] Prepare six replicates of spiked sample solutions at the 100% limit level by another researcher at different times. The RSD of the recovery rates of the six 100% spiked sample solutions prepared by the second researcher is not more than 15.0%, and the RSD of the recovery rates of the twelve spiked sample solutions is not more than 30.0%. The intermediate precision test results are shown in Table 9.

[0080] Table 9 Results of the intermediate precision test

[0081]

[0082] 9. Solution stability

[0083] Prepare one replicate of a control solution and one replicate of a spiked sample solution at the 100% limit level, respectively, and analyze these solutions at 24 hours or other time periods, and compare them with the freshly prepared solutions. The content of the stability solution is between 70.0% and 130.0% of the initial content. The verification results are shown in Table 10 below:

[0084] Table 10 Solution stability results

[0085]

[0086] 10. Robustness

[0087] The injection port temperature, initial column temperature, and flow rate were changed respectively, and two 100% level spiked sample solutions were prepared, each condition was injected once, and the RSD of the peak area of 6 tests under a single condition in the robustness condition was not greater than 20.0%. The verification results are shown in Table 11 below:

[0088] Table 11 Chloroacetamide robustness results

[0089] Injection Port Temperature ± 2 °C Peak Area Initial Column Temperature ± 2 °C Peak Area Flow Rate ± 0.02 ml / min Peak Area Original Conditions (250 °C) 105.461 Original Conditions (50 °C) 105.461 Original Conditions (1.50 105.461 Original Conditions (250 °C) 116.733 Original Conditions (50 °C) 116.733 Original Conditions (1.50 116.733 Injection Port Temperature 109.970 Initial Column Temperature (48 °C) 105.712 Flow Rate (1.48 ml / min) 113.644 Injection Port Temperature 118.320 Initial Column Temperature (48 °C) 113.143 Flow Rate (1.48 ml / min) 117.234 Injection Port Temperature 114.447 Initial Column Temperature (52 °C) 119.806 Flow Rate (1.52 ml / min) 114.303 Injection Port Temperature 127.839 Initial Column Temperature (52 °C) 128.006 Flow Rate (1.52 ml / min) 121.801 RSD (%) 6.6 RSD (%) 7.6 RSD (%) 4.7

[0090] Step four: calculate the results according to the following formula:

[0091] (1) Response factor

[0092] The response factor is calculated according to the following formula

[0093]

[0094] In the formula:

[0095] A STD Refers to the average peak area of the analyte in the initial 6 control solution

[0096] C STD Refers to the concentration of the analyte in the control solution (ng / ml)

[0097] RF refers to the response factor of the analyte

[0098] (2) Residual calculation

[0099] The residual amount of the analyte is calculated according to the following formula:

[0100]

[0101] In the formula:

[0102] A SPL Refers to the peak area of the analyte in the sample chromatogram

[0103] W SPL Refers to the sample weight (mg)

[0104] V SPL Refers to the dilution volume of the sample (ml)

[0105] RF refers to the response factor of the analyte

[0106] The results are shown in Table 12 below:

[0107] Table 12 Sample test results

[0108]

[0109] Example 2

[0110] Example 2 provides a method for detecting chloroacetamide residues in piracetam.

[0111] Example 2 differs from Example 1 in that the temperature rising program in the gas chromatography conditions is different, as shown below.

[0112] The parameters of the gas chromatography are as follows: the injection port temperature is 255°C; the temperature rising program is as follows: the initial temperature is 55°C, the temperature is raised to 285°C at a temperature rising rate of 45°C / min, the post-run temperature is 305°C, and the post-run time is 5.5 min; the parameter conditions of the gas chromatography also include: the carrier gas flow rate is 1.8 ml / min; the injection volume is 1.2 μl; the split mode is split, and the split ratio is 12:1; the control mode is constant flow; and the carrier gas is He.

[0113] The mass spectrometry parameters are as follows: the ion source temperature is 235°C, the quadrupole temperature is 155°C, and the transfer line temperature is 255°C; the sampling mode is MRM, and the ion source is EI; the solvent delay is 2.5 min, and the time is 5.00 min. The scanning parameters of the mass spectrometry are as follows: the parent ion is 93 m / z, and the daughter ion is 44 m / z; the CE is 15 V, and the Dwell is 210 ms.

[0114] The results of the specificity test are as follows:

[0115] The results show that no target peak is detected in the chromatogram of the blank solution, which does not interfere with the detection; the target peak is shown in the chromatogram of the test sample solution, and no adjacent peak with a peak area greater than the LOQ is detected; the target peak is shown in the chromatogram of the 100% limit concentration reference substance solution; the target peak is shown in the chromatogram of the 100% limit concentration spiked test sample solution, and no adjacent peak with a peak area greater than the LOQ is detected; the results meet the requirements, and the method has good specificity.

[0116] Example 3

[0117] Example 3 provides a method for detecting chloroacetamide residues in piracetam.

[0118] Example 3 differs from Example 1 in that the temperature rising program in the gas chromatography conditions is different, as shown below.

[0119] The parameters of the gas chromatograph are as follows: injection port temperature: 245 ℃; temperature rising program: initial temperature of 45 ℃, rising to 275 ℃ at a rate of 35 ℃ / min, and then running at 295 ℃ for 4.5 min; the parameter conditions of the gas chromatograph also include: carrier gas flow rate: 1.2 ml / min; injection volume: 0.8 μl; split mode: split, split ratio of 8:1; control mode: constant flow; carrier gas: He.

[0120] The mass spectrometry parameters are as follows: ion source temperature of 225 ℃, quadrupole temperature of 145 ℃, and transfer line temperature of 245 ℃; sampling mode: MRM, ion source: EI; solvent delay of 1.5 min, and time of 2.00 min. The scanning parameters of the mass spectrometry are as follows: parent ion of 93 m / z, daughter ion of 44 m / z; CE of 14 V, and Dwell of 190 ms.

[0121] The specificity test results are as follows:

[0122] The results show that no target peak is detected in the chromatogram of the blank solution, which does not interfere with the detection; the target peak is shown in the chromatogram of the test sample solution, and no adjacent peak with a peak area greater than LOQ is detected; the target peak is shown in the chromatogram of the 100% limit concentration reference substance solution; the target peak is shown in the chromatogram of the 100% limit concentration spiked test sample solution, and no adjacent peak with a peak area greater than LOQ is detected; the results meet the requirements, and the method has good specificity.

[0123] Comparative Example

[0124] Comparative Example 1

[0125] Comparative Example 1 provides a method for detecting chloroacetamide residues in piracetam.

[0126] Comparative Example 1 and Example 1 differ in the temperature rising program in the gas chromatography conditions, which are shown as follows.

[0127] Chromatographic column: HP-1MS UI (30 m x 0.25 mm x 1.0 μm);

[0128] Injection port temperature: 230 ℃; flow rate: 1.0 ml / min; injection volume: 1.0 μl; split mode: split, split ratio of 5:1; control mode: constant flow; carrier gas: He; temperature rising program: initial temperature of 30 ℃, rising to 250 ℃ at a rate of 30 ℃ / min.

[0129] The specificity test results are as follows:

[0130] The results show that the test sample interferes with the detection of the target peak.

[0131] Comparative Example 2

[0132] Comparative Example 2 provides a method for detecting the residual chloroacetamide in piracetam.

[0133] Comparative Example 2 differs from Example 1 in that the temperature rising program in the gas chromatography condition is different, which is shown as follows.

[0134] The gas chromatography condition is as follows:

[0135] The chromatographic column is HP-1MS UI (30 m x 0.25 mm x 1.0 μm);

[0136] The injection port temperature is 270 °C; the flow rate is 1.0 ml / min; the injection volume is 1 μl; the split mode is split, with a split ratio of 15:1; the control mode is constant flow; the carrier gas is He; and the temperature rising program is that the initial temperature is 60 °C, and the temperature is raised to 300 °C at a temperature rising rate of 60 °C / min.

[0137] The specificity detection result is as follows:

[0138] The result shows that the test sample interferes with the detection of the target peak.

[0139] Comparative Example 3

[0140] Comparative Example 3 provides a method for detecting the residual chloroacetamide in piracetam.

[0141] Comparative Example 3 differs from Example 1 in that the temperature rising program in the gas chromatography condition is different, which is shown as follows.

[0142] The gas chromatography condition is as follows:

[0143] The chromatographic column is HP-1MS UI (30 m x 0.25 mm x 1.0 μm);

[0144] The injection port temperature is 230 °C; the flow rate is 0.5 ml / min; the injection volume is 1.5 μl; the split mode is split, with a split ratio of 10:1; the control mode is constant flow; the carrier gas is He; and the temperature rising program is that the initial temperature is 30 °C, and the temperature is raised to 240 °C at a temperature rising rate of 30 °C / min.

[0145] The specificity detection result is as follows:

[0146] The result shows that the test sample interferes with the detection of the target peak.

[0147] Comparative Example 4

[0148] Comparative Example 4 provides a method for detecting the residual chloroacetamide in piracetam.

[0149] Comparative Example 4 differs from Example 1 in that the parameter condition of mass spectrometry is different, which is shown as follows.

[0150] The parameter conditions of mass spectrum are: acquisition type: MRM; ion source: EI; solvent delay: 1.0 min; transfer line temperature: 235°C; quadrupole temperature: 200°C; ion source temperature: 230°C.

[0151] Specificity test results:

[0152] The results show that there is no target peak detected.

[0153] Although the present application has been described in detail with general description and specific embodiments above, some modifications or improvements can be made on the basis of the present application, which is obvious to those skilled in the art. Therefore, these modifications or improvements made on the basis of not deviating from the spirit of the present application, all belong to the scope of the present application claimed.

Claims

1. A method for detecting residual chloroacetamide in piracetam, characterized by, The sample to be detected is detected by gas chromatography-triple quadrupole mass spectrometry GC-MS / MS; The parameters of the gas chromatography are as follows: the injection port temperature is 245-255 DEG C; the temperature rising program is that the initial temperature is 45-55 DEG C, the temperature is raised to 275-285 DEG C at a temperature rising rate of 35-45 DEG C / min, and the post-run temperature is 295-305 DEG C, and the post-run time is 4.5-5.5 min; The parameters of the mass spectrometry are as follows: the ion source temperature is 225-235 DEG C, the quadrupole temperature is 145-155 DEG C, and the transfer line temperature is 245-255 DEG C; the sampling mode is MRM, the ion source is EI; the solvent delay is 1.5-2.5 min, and the time is 2.00-5.00 min.

2. The method for detecting residual chloroacetamide in piracetam according to claim 1, characterized in that, The temperature rising program is that the initial temperature is 50 DEG C, the temperature is raised to 280 DEG C at a temperature rising rate of 40 DEG C / min, the post-run temperature is 300 DEG C, and the post-run time is 5 min.

3. The method for detecting residual chloroacetamide in piracetam according to claim 1, characterized in that, The chromatographic column of the gas chromatography conditions is HP-1MS UI, 30 m*0.25 mm*1.0 mu m.

4. The method of claim 1, wherein the piracetam is characterized by the presence of a chloroacetamide residue. The parameter conditions of the gas chromatography further include that the carrier gas flow rate is 1.2-1.8 ml / min, the injection volume is 0.8-1.2 mu l, the split mode is split, the split ratio is 8-12:1, the control mode is constant flow, and the carrier gas is He.

5. The method of claim 1, wherein the piracetam is characterized by the presence of a chloroacetamide residue. The parameter conditions of the mass spectrometry are as follows: the solvent delay is 2 min, the transfer line temperature is 250 DEG C, the quadrupole temperature is 150 DEG C, and the ion source temperature is 230 DEG C.

6. The method of claim 1, wherein the piracetam is characterized by the presence of a chloroacetamide residue. The scanning parameters of the mass spectrometry are as follows: the parent ion is 93 m / z, the daughter ion is 44 m / z, the CE is 14-15 V, and the Dwell is 190-210 ms.

7. The method of claim 1, wherein the piracetam is characterized by the presence of a chloroacetamide residue. The detection limit of the chloroacetamide is 0.00938 ppm, and the quantification limit of the chloroacetamide is 0.0188 ppm.

8. The method for detecting residual chloroacetamide in piracetam according to any one of claims 1 to 7, characterized in that, The solution to be detected includes a control substance stock solution, a control substance solution, a sensitivity solution and a test sample solution.

9. The method of claim 8, wherein the piracetam is selected from the group consisting of piracetam, oxiracetam, aniracetam, pramiracetam, nebracetam, coluracetam, and idacram. The preparation method of the piracetam test sample solution is as follows: 80 mg of piracetam raw material is placed in a 15 ml centrifuge tube, 2.0 ml of methanol is added, ultrasonic dissolution is carried out, and mixing is carried out to obtain the piracetam test sample solution.

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