Search

CN-122017067-A - Detection method of nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidinecarboxamide in ropivacaine hydrochloride

CN122017067ACN 122017067 ACN122017067 ACN 122017067ACN-122017067-A

Abstract

The invention discloses a detection method of nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidine formamide in ropivacaine hydrochloride, which comprises the following steps of weighing ropivacaine hydrochloride, adding water to dissolve to obtain a sample solution, weighing a reference substance of nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidine formamide, dissolving and diluting with methanol to obtain a reference substance solution, weighing the sample solution and the reference substance solution, injecting the sample solution and the reference substance solution into a high performance liquid chromatography-tandem mass spectrometer, recording a chromatogram, and calculating with peak area according to an external standard method. According to the invention, the content of the nitrogen nitroso- (S) - (-) -N- (2, 6-dimethyl phenyl) -2-piperidine formamide in ropivacaine hydrochloride is determined by a high performance liquid chromatography-tandem mass spectrometry combined instrument method, and the method is simple, convenient and feasible, and has the advantages of strong specificity, high accuracy, good repeatability and high detection sensitivity.

Inventors

  • ZHU JUN
  • Hu Tingdan
  • CHENG XIN
  • HUANG PING
  • LUO JINJIN
  • JIANG LU

Assignees

  • 湖南科伦制药有限公司

Dates

Publication Date
20260512
Application Date
20260204

Claims (7)

  1. 1. The detection method of the nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidinecarboxamide in ropivacaine hydrochloride is characterized by comprising the following steps of: Weighing ropivacaine hydrochloride, and adding water for dissolution to obtain a sample solution; weighing a nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidine formamide reference substance, and dissolving and diluting the reference substance with methanol to obtain a reference substance solution; measuring the sample solution and the reference substance solution, injecting the sample solution and the reference substance solution into a high performance liquid chromatography-tandem mass spectrometer, recording a chromatogram, and calculating according to an external standard method and peak areas; the analytical concentration was 0.352ng/ml of the nitrogen-containing nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidinecarboxamide control.
  2. 2. The method for detecting nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidinecarboxamide in ropivacaine hydrochloride according to claim 1, wherein the filler of the high performance liquid chromatography-tandem mass spectrometry analysis column is octadecylsilane chemically bonded silica, the mobile phase is a combined 0.1% formic acid aqueous solution and 0.1% formic acid methanol solution, the column temperature is 35 ℃, the flow rate is 0.5ml per minute, and the sample injection volume is 10 μl.
  3. 3. The method for detecting nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidinecarboxamide in ropivacaine hydrochloride according to claim 2, wherein the mobile phase elution mode is as follows: 。
  4. 4. A method for detecting ropivacaine hydrochloride according to claim 3 wherein the analytical column has an inner diameter of 4.6mm, a length of 100mm and a filler particle size of 3 μm.
  5. 5. The method for detecting nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidinecarboxamide in ropivacaine hydrochloride according to claim 4, wherein the high performance liquid chromatography-tandem mass spectrometer is used for primary mass spectrometry selection of ion 262.3, secondary mass spectrometry of ion 140.9, acceleration voltage of 75V and collision energy of 5V.
  6. 6. The method for detecting nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidinecarboxamide in ropivacaine hydrochloride according to claim 5, wherein the ion source parameters of the high performance liquid chromatography-tandem mass spectrometer are as follows: Drying gas temperature 250 ℃, gas flow rate 5L/min, atomizer pressure 25 psi, sheath gas temperature 150 ℃, sheath gas flow rate 8L/min, capillary voltage 4000V, nozzle voltage 0V.
  7. 7. The method for detecting nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidinecarboxamide in ropivacaine hydrochloride according to claim 6, wherein the scanning parameters of the high performance liquid chromatography-tandem mass spectrometer are as follows: polarity positive ion mode, scanning type Multiple Reaction Monitoring (MRM), scanning time 7.5 minutes, collision cell acceleration voltage 5V.

Description

Detection method of nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidinecarboxamide in ropivacaine hydrochloride Technical Field The invention relates to the field of anesthetic production, in particular to a detection method of nitrogen nitroso- (S) - (-) -N- (2, 6-dimethyl phenyl) -2-piperidine formamide in ropivacaine hydrochloride. Background Ropivacaine hydrochloride is suitable for surgical anesthesia, such as epidural anesthesia, including caesarean section, subarachnoid anesthesia, regional retardation, or for acute pain management, such as continuous epidural infusion or intermittent single use, such as postoperative or vaginal delivery analgesia, regional retardation. The nitrogen nitroso- (S) - (-) -N- (2, 6-dimethyl phenyl) -2-piperidine formamide is generated in the synthesizing process of ropivacaine hydrochloride, and is a genotoxic impurity, the content of which is required to be strictly controlled, so that a development method is used for content determination. At present, no method for detecting the content of nitrogen nitroso- (S) - (-) -N- (2, 6-dimethyl phenyl) -2-piperidinecarboxamide in ropivacaine hydrochloride exists in pharmacopoeia and literature of each country. Disclosure of Invention The invention aims to provide a method for detecting nitrogen nitroso- (S) - (-) -N- (2, 6-dimethyl phenyl) -2-piperidine formamide in ropivacaine hydrochloride, which has high sensitivity and accuracy. The invention provides a detection method of nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidinecarboxamide in ropivacaine hydrochloride, which comprises the following steps: Weighing ropivacaine hydrochloride, and adding water for dissolution to obtain a sample solution; weighing a nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidine formamide reference substance, and dissolving and diluting the reference substance with methanol to obtain a reference substance solution; Measuring the sample solution and the reference substance solution, injecting the sample solution and the reference substance solution into a high performance liquid chromatography-tandem mass spectrometer, recording a chromatogram, and calculating according to an external standard method and peak areas. In the method for detecting the nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidinecarboxamide in ropivacaine hydrochloride, preferably, the filler of the analysis column of the high performance liquid chromatography-tandem mass spectrometer is octadecylsilane chemically bonded silica, a mobile phase is a combined 0.1% formic acid aqueous solution and 0.1% formic acid methanol solution, the column temperature is 35 ℃, the flow rate is 0.5ml per minute, and the sample injection volume is 10 μl. The detection method of the nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidinecarboxamide in ropivacaine hydrochloride preferably comprises the following steps of: In the method for detecting the nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidinecarboxamide in ropivacaine hydrochloride, the inner diameter of the analysis column is preferably 4.6mm, the length is preferably 100mm, and the particle size of the filling agent is preferably 3 mu m. In the method for detecting the nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidinecarboxamide in ropivacaine hydrochloride, preferably, the high performance liquid chromatography-tandem mass spectrometer is used for carrying out primary mass spectrometry selection ion 262.3, secondary mass spectrometry selection ion 140.9, acceleration voltage is 75V and collision energy is 5V. In the method for detecting the nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidinecarboxamide in ropivacaine hydrochloride, preferably, the ion source parameters of the high performance liquid chromatography-tandem mass spectrometer are as follows: Drying gas temperature 250 ℃, gas flow rate 5L/min, atomizer pressure 25 psi, sheath gas temperature 150 ℃, sheath gas flow rate 8L/min, capillary voltage 4000V, nozzle voltage 0V. In the method for detecting the nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidinecarboxamide in ropivacaine hydrochloride, preferably, the scanning parameters of the high performance liquid chromatography-tandem mass spectrometer are as follows: polarity positive ion mode, scanning type Multiple Reaction Monitoring (MRM), scanning time 7.5 minutes, collision cell acceleration voltage 5V. The beneficial effects are that: According to the method for detecting the nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidinecarboxamide in ropivacaine hydrochloride, provided by the invention, a high performance liquid chromatography-tandem mass spectrometry is adopted, a secondary mass spectrometry method is adopted, the secondary characteristic charge ratio of the nitrogen nitroso- (S) - (-) -N- (2, 6-dimethylphenyl) -2-piperidinecarboxamide is used as detecti