Method for determining residual N,N-dimethylacetamide solvent in bulk drug

Abstract

The invention discloses a method for determining a residual N,N-dimethylacetamide solvent in a bulk drug. The method comprises the following steps: (1) preparing a medium-polarity capillary chromatographic column and a flame ionization detector and setting a temperature control mode of primary programmed heating and secondary programmed heating; (2) adding a diluent into the bulk drug so as to prepare a to-be-determined sample solution; (3) adding a diluent into N,N-dimethylacetamide so as to prepare a to-be-determined control solution; and (4) directly injecting the to-be-determined sample solution and the to-be-determined control solution into a gas chromatograph so as to finish determination of the residual N,N-dimethylacetamide solvent. According to the invention, the manners of programmed heating and direct sample introduction are employed for detection so as to prevent target peaks from interference by blank peaks, so detection accuracy is improved; the method realizes rapid high-efficiency separation and content determination of residual N,N-dimethylacetamide in the bulk drug; and the method is strong in specificity, high in precision and accuracy and convenient to operate, so medicine quality is effectively controlled.

Description

technical field

[0001] The invention relates to the field of chemical analysis, in particular, the invention relates to a method for determining N,N-dimethylacetamide solvent residue in raw materials. Background technique

[0002] N,N-Dimethylacetamide (N,N-Dimethylacetamide, DMAc) is a colorless transparent liquid, which can be freely miscible with organic solvents such as water, alcohol, ether, benzene and chloroform, and can be dissolved in anhydrous, acid, It has good stability under alkaline conditions, with a boiling point of 165-166°C. Used as a raw material for synthetic fibers and an excellent polar solvent for organic synthesis.

[0003] In drug synthesis, N,N-dimethylacetamide is often used as an excellent polar solvent, which can be used as a common solvent for the synthesis of various active pharmaceutical ingredients (API, Active Pharmaceutical Ingredient) such as vonoprazan fumarate, but due to its Due to the existence of certain toxicity, ICH guideline Q3C ...

Examples

Embodiment 1

[0054]

[0055]

[0056] Diluent: N-Methylpyrrolidone

[0057] Experimental steps:

[0058] Need testing solution: take 1 g of vonoprazan fumaric acid crude drug, accurately weigh it, place it in a 10ml measuring bottle, shake to dissolve the fumaric acid vonoprazan crude drug completely, then dilute to the scale, shake well, Instantly.

[0059] N,N-dimethylacetamide reference substance solution: Take about 109mg of N,N-dimethylacetamide, weigh it accurately, put it in a 100ml measuring bottle, dissolve it with diluent and dilute to the mark, shake well, and use it as a control stock solution; accurately measure 1ml of the stock solution of the reference substance, put it in a 10ml measuring bottle, dilute to the mark with diluent, and shake well. (109μg / ml)

[0060] Trace amount of N,N-dimethylacetamide reference substance solution: Accurately measure 1ml of the reference substance solution, put it in a 25ml measuring bottle, dilute to the mark with diluent, and shake ...

Embodiment 2

[0065]

[0066]

[0067] Diluent: N-Methylpyrrolidone

[0068] Experimental steps:

[0069] Need testing solution: take 1 g of vonoprazan fumaric acid crude drug, accurately weigh it, place it in a 10ml measuring bottle, shake to dissolve the fumaric acid vonoprazan crude drug completely, then dilute to the scale, shake well, Instantly.

[0070] N,N-dimethylacetamide reference substance solution: Take about 109mg of N,N-dimethylacetamide, weigh it accurately, put it in a 100ml measuring bottle, dissolve it with diluent and dilute to the mark, shake well, and use it as a control stock solution; accurately measure 1ml of the stock solution of the reference substance, put it in a 10ml measuring bottle, dilute to the mark with diluent, and shake well. (109μg / ml)

[0071] 100% sample recovery solution: Take about 1g of the sample, weigh it accurately, put it in a 10ml measuring bottle, add the reference substance solution to dissolve and dilute to the mark, shake well, and...

Embodiment 3

[0074]

[0075]

[0076] Diluent: N-Methylpyrrolidone

[0077] Experimental steps:

[0078] Need testing solution: take 1 g of vonoprazan fumaric acid crude drug, accurately weigh it, place it in a 10ml measuring bottle, shake to dissolve the fumaric acid vonoprazan crude drug completely, then dilute to the scale, shake well, Instantly.

[0079] N,N-dimethylacetamide reference substance solution: Take about 109mg of N,N-dimethylacetamide, weigh it accurately, put it in a 100ml measuring bottle, dissolve it with diluent and dilute to the mark, shake well, and use it as a control stock solution; accurately measure 1ml of the stock solution of the reference substance, put it in a 10ml measuring bottle, dilute to the mark with diluent, and shake well. (109μg / ml)

[0080] Trace amount of N,N-dimethylacetamide reference substance solution: Accurately measure 1ml of the reference substance solution, put it in a 25ml measuring bottle, dilute to the mark with diluent, and shak...

technical field

[0001] The invention relates to the field of chemical analysis, in particular, the invention relates to a method for determining N,N-dimethylacetamide solvent residue in raw materials. Background technique

[0002] N,N-Dimethylacetamide (N,N-Dimethylacetamide, DMAc) is a colorless transparent liquid, which can be freely miscible with organic solvents such as water, alcohol, ether, benzene and chloroform, and can be dissolved in anhydrous, acid, It has good stability under alkaline conditions, with a boiling point of 165-166°C. Used as a raw material for synthetic fibers and an excellent polar solvent for organic synthesis.

[0003] In drug synthesis, N,N-dimethylacetamide is often used as an excellent polar solvent, which can be used as a common solvent for the synthesis of various active pharmaceutical ingredients (API, Active Pharmaceutical Ingredient) such as vonoprazan fumarate, but due to its Due to the existence of certain toxicity, ICH guideline Q3C ...

Examples

Embodiment 1

[0054]

[0055]

[0056] Diluent: N-Methylpyrrolidone

[0057] Experimental steps:

[0058] Need testing solution: take 1 g of vonoprazan fumaric acid crude drug, accurately weigh it, place it in a 10ml measuring bottle, shake to dissolve the fumaric acid vonoprazan crude drug completely, then dilute to the scale, shake well, Instantly.

[0059] N,N-dimethylacetamide reference substance solution: Take about 109mg of N,N-dimethylacetamide, weigh it accurately, put it in a 100ml measuring bottle, dissolve it with diluent and dilute to the mark, shake well, and use it as a control stock solution; accurately measure 1ml of the stock solution of the reference substance, put it in a 10ml measuring bottle, dilute to the mark with diluent, and shake well. (109μg / ml)

[0060] Trace amount of N,N-dimethylacetamide reference substance solution: Accurately measure 1ml of the reference substance solution, put it in a 25ml measuring bottle, dilute to the mark with diluent, and shake ...

Embodiment 2

[0065]

[0066]

[0067] Diluent: N-Methylpyrrolidone

[0068] Experimental steps:

[0069] Need testing solution: take 1 g of vonoprazan fumaric acid crude drug, accurately weigh it, place it in a 10ml measuring bottle, shake to dissolve the fumaric acid vonoprazan crude drug completely, then dilute to the scale, shake well, Instantly.

[0070] N,N-dimethylacetamide reference substance solution: Take about 109mg of N,N-dimethylacetamide, weigh it accurately, put it in a 100ml measuring bottle, dissolve it with diluent and dilute to the mark, shake well, and use it as a control stock solution; accurately measure 1ml of the stock solution of the reference substance, put it in a 10ml measuring bottle, dilute to the mark with diluent, and shake well. (109μg / ml)

[0071] 100% sample recovery solution: Take about 1g of the sample, weigh it accurately, put it in a 10ml measuring bottle, add the reference substance solution to dissolve and dilute to the mark, shake well, and...

Embodiment 3

[0074]

[0075]

[0076] Diluent: N-Methylpyrrolidone

[0077] Experimental steps:

[0078] Need testing solution: take 1 g of vonoprazan fumaric acid crude drug, accurately weigh it, place it in a 10ml measuring bottle, shake to dissolve the fumaric acid vonoprazan crude drug completely, then dilute to the scale, shake well, Instantly.

[0079] N,N-dimethylacetamide reference substance solution: Take about 109mg of N,N-dimethylacetamide, weigh it accurately, put it in a 100ml measuring bottle, dissolve it with diluent and dilute to the mark, shake well, and use it as a control stock solution; accurately measure 1ml of the stock solution of the reference substance, put it in a 10ml measuring bottle, dilute to the mark with diluent, and shake well. (109μg / ml)

[0080] Trace amount of N,N-dimethylacetamide reference substance solution: Accurately measure 1ml of the reference substance solution, put it in a 25ml measuring bottle, dilute to the mark with diluent, and shak...

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