Method for detecting genotoxic impurity haloalkane in aripiprazole

A detection method, aripiprazole technology, is applied in the field of detection of genotoxic impurity halogenated alkanes in aripiprazole, which can solve the problems of low limit, difficult analysis, no detection method of halogenated alkanes, etc., and achieve good durability , good specificity, good theoretical plate number and symmetry factor

Active Publication Date: 2020-12-22
YANGTZE RIVER PHARM GRP NANJING HAILING PHARM CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] Through inquiries, there is no detection method for halogenated alkanes in aripiprazole in pharmacopoeias of various countries, and the maximum daily dose of aripiprazole is 30 mg, and the general threshold specified in the guidelines for the limit of genotoxic impurities is 1.5 μg / day, passed In conversion, the limit concentration of each halogenated alkanes is 50ppm, due to the low limit, the analysis is more difficult

Method used

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  • Method for detecting genotoxic impurity haloalkane in aripiprazole
  • Method for detecting genotoxic impurity haloalkane in aripiprazole
  • Method for detecting genotoxic impurity haloalkane in aripiprazole

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Experimental program
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Effect test

Embodiment 1

[0075] Specificity and system suitability experiment:

[0076] The conditions of gas chromatography-mass spectrometry detection in the present embodiment are:

[0077] Gas chromatography conditions: direct injection: 1 μL; chromatographic column: a capillary column with 6% cyanopropylphenyl-94% dimethyl polysiloxane (or similar in polarity)) as a stationary liquid as a chromatographic column (Agilent DB -624, 30m×0.25mm×1.4μm); carrier gas is helium; flow rate: 1.0mL / min; temperature program: the initial temperature is 100°C, keep it for 5 minutes, and raise the temperature to 150°C at a rate of 5°C per minute, and maintain 2 minutes; inlet temperature 180°C; split ratio 10:1;

[0078] Mass spectrometry conditions: transfer line temperature 200°C, ion source temperature 230°C, quadrupole temperature 150°C, ion monitoring mode (SIM), extracted ions are m / z55.00; m / z91.00; m / z135.00, stationed Dwell time 100ms, solvent delay time 4 minutes, low resolution mode.

[0079] Exclu...

Embodiment 2

[0088] Durability test:

[0089] The preparation method of the aripiprazole-halogenated alkane mixed solution is the same as that of Example 1.

[0090] The flow rate in the gas chromatographic conditions is respectively set to 0.9mL / min and 1.1mL / min, and other conditions are consistent with embodiment 1, and the aripiprazole-halogenated alkane mixed solution is carried out to gas chromatography-mass spectrometry detection, and the obtained spectrum is as follows Figure 8 ~ Figure 9 shown;

[0091] Set the initial temperature of the chromatographic column in the gas chromatography conditions to 98°C and 102°C respectively, and the other conditions are the same as in Example 1, and the aripiprazole-halogenated alkane mixture is detected by gas chromatography-mass spectrometry, and the obtained spectrum is as follows Figure 10 ~ Figure 11 shown.

[0092] The split ratios in the gas chromatographic conditions are respectively set to be 9:1 and 11:1, and other conditions are ...

Embodiment 3

[0095] Solution stability testing:

[0096] The preparation method of need testing solution and reference substance solution is identical with embodiment 1, respectively at 0h, 2h, 4h, 6h, 8h, 12h, 16h and 24h need testing solution and reference substance solution are carried out gas chromatography-mass spectrometry detection , detection condition is identical with embodiment 1, and gained result is shown in table 2:

[0097] Table 2 Aripiprazole solution and reference substance solution stability test result

[0098]

[0099] According to Table 2, it can be seen that the deviation of the peak area and 0h of the reference substance solution and the test solution within 24h is less than 20%, indicating that the two can be kept stable for 24h.

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Abstract

The invention relates to the technical field of drug quality detection, and provides a method for detecting genotoxic impurity haloalkane in aripiprazole, wherein the method comprises the steps: firstly, preparing an aripiprazole test solution and a reference solution containing 1,4-dichlorobutane, 1-bromo-4-chlorobutane and 1,4-dibromo-butane, detecting by gas chromatography-mass spectrometry, and calculating to obtain the contents of 1,4-dichlorobutane, 1-bromo-4-chlorobutane and 1,4-dibromo-butane in aripiprazole by an external standard method. The method provided by the invention is good in specificity, good in durability, capable of accurately detecting each genotoxic impurity in aripiprazole, relatively good in separation degree of peaks, theoretical plate number and trailing factorsymmetry factor, and high in response.

Description

technical field [0001] The invention relates to the technical field of drug quality detection, in particular to a detection method for genotoxic impurity halogenated alkanes in aripiprazole. Background technique [0002] Aripiprazole is a new type of atypical antischizophrenia drug, which has a bidirectional regulation effect on the DA nervous system and is a stabilizer of DA transmitters. It has high affinity with D2, D3, 5-HT1A and 5-HT2A receptors, and produces anti-schizophrenia effect through partial agonism on D2 and 5-HT1A receptors and antagonism on 5-HT2A receptors . [0003] In alkane molecules, the hydrogen atoms are partially or completely replaced by halogen atoms to form compounds called haloalkane, or haloalkane for short. As an important organic solvent and product intermediate, halogenated alkanes are widely used in many industries, but they are often carcinogenic, teratogenic and mutagenic substances. Therefore, as human beings pay more and more attention...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02
CPCG01N30/02G01N2030/047
Inventor 徐润贾玉荣赵道松卓敏
Owner YANGTZE RIVER PHARM GRP NANJING HAILING PHARM CO LTD
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