Method for determining cumene hydroperoxide impurity

Abstract

The invention discloses a method for determining a cumene hydroperoxide impurity. The method comprises the step of carrying out gradient elution by selecting a siloxane bonded silica gel as a stationary phase and a first mixed solvent of an organic solution and an alkaline aqueous solution as a mobile phase. The detection method is strong in specificity, high in precision, strong in accuracy and simple, convenient and quick to operate, and the quality of a drug can be effectively controlled. The method is wide in applicability and can be used for detecting a cumene hydroperoxide compound in medicinal raw materials such as right-handed lansoprazole and the like.

Description

technical field

[0001] The invention relates to the field of chemical analysis, in particular, the invention relates to a method for measuring impurities in cumene hydroperoxide. Background technique

[0002] Cumene Hydroperoxide (CHP) is a colorless or light yellow liquid, soluble in alcohols, ketones, esters, hydrocarbons, slightly soluble in water, with a boiling point of 153°C. CHP has been widely used in the fields of fine chemicals, polymer materials, and organic synthesis. It can be used as an initiator for chain autooxidation and polymerization reactions, an accelerator for rubber vulcanization, and an oxidant for organic compounds. It is also commonly used in the production of phenol.

[0003] In drug synthesis, cumene hydroperoxide is often used as an asymmetric oxidant, which can be used as various raw materials (API, Active Pharmaceutical Ingredient) such as dexlansoprazole, esomeprazole, and levopantoprazole sodium. ) synthetic key material, but due to its geno...

Examples

Embodiment 1

[0051] Instrument: Agilent1260 high performance liquid chromatography, 1210 ultraviolet detector

[0052] Chromatographic column: a chromatographic column (150×4.6mm, 5μm) filled with siloxane-bonded silica gel;

[0053] Mobile phase A: triethylamine aqueous solution (adjust pH to 6.2 with phosphoric acid)

[0054] Mobile Phase B: Acetonitrile

[0055] Gradient elution:

[0056] time / min

Mobile phase A / %

Mobile phase B / %

0

85

15

3

85

15

35

45

55

36

85

15

45

85

15

[0057] Flow rate: 1.0ml / min

[0058] Detection wavelength: 210nm

[0059] Column temperature: 30°C

[0060] Injection volume: 10μl

[0061] Diluent: acetonitrile: triethylamine aqueous solution (adjust pH to 10-11 with phosphoric acid) = 40:60 (v / v)

[0062] Run time: 45 minutes

[0063] Experimental steps:

[0064] Need testing solution: take by weighing dexlansoprazole crude drug 1.0014g and put 10mL measuri...

Embodiment 2

[0071] Instrument: Agilent1260 high performance liquid chromatography, 1210 ultraviolet detector

[0072] Chromatographic column: a chromatographic column (150×4.6mm, 5μm) filled with siloxane-bonded silica gel;

[0073] Mobile phase A: triethylamine aqueous solution (adjust pH to 5.5 with phosphoric acid)

[0074] Mobile Phase B: Acetonitrile

[0075] Gradient elution:

[0076] time / min

Mobile phase A / %

Mobile phase B / %

0

85

15

3

85

15

35

45

55

36

85

15

45

85

15

[0077] Flow rate: 1.2ml / min

[0078] Detection wavelength: 210nm

[0079] Column temperature: 30°C

[0080] Injection volume: 10μl

[0081] Diluent: acetonitrile: triethylamine aqueous solution (adjust pH to 10-11 with phosphoric acid) = 40:60 (v / v)

[0082] Run time: 45 minutes

[0083] Experimental steps:

[0084] Cumyl hydroperoxide reference stock solution: use a diluent to prepare a solution with a concen...

Embodiment 3

[0090] Instrument: Agilent1260 high performance liquid chromatography, 1210 ultraviolet detector

[0091] Chromatographic column: a chromatographic column (150×4.6mm, 5μm) filled with siloxane-bonded silica gel;

[0092] Mobile phase A: triethylamine aqueous solution (adjust pH to 7.0 with phosphoric acid)

[0093] Mobile Phase B: Methanol

[0094] Gradient elution:

[0095] time / min

Mobile phase A / %

Mobile phase B / %

0

85

15

3

85

15

35

45

55

36

85

15

45

85

15

[0096] Flow rate: 0.8ml / min

[0097] Detection wavelength: 210nm

[0098] Column temperature: 30°C

[0099] Injection volume: 10μl

[0100] Diluent: acetonitrile: triethylamine aqueous solution (adjust pH to 10-11 with phosphoric acid) = 40:60 (v / v)

[0101] Run time: 45 minutes

[0102] Experimental steps:

[0103] Cumyl hydroperoxide reference stock solution: use a diluent to prepare a solution with a concentrat...

technical field

[0001] The invention relates to the field of chemical analysis, in particular, the invention relates to a method for measuring impurities in cumene hydroperoxide. Background technique

[0002] Cumene Hydroperoxide (CHP) is a colorless or light yellow liquid, soluble in alcohols, ketones, esters, hydrocarbons, slightly soluble in water, with a boiling point of 153°C. CHP has been widely used in the fields of fine chemicals, polymer materials, and organic synthesis. It can be used as an initiator for chain autooxidation and polymerization reactions, an accelerator for rubber vulcanization, and an oxidant for organic compounds. It is also commonly used in the production of phenol.

[0003] In drug synthesis, cumene hydroperoxide is often used as an asymmetric oxidant, which can be used as various raw materials (API, Active Pharmaceutical Ingredient) such as dexlansoprazole, esomeprazole, and levopantoprazole sodium. ) synthetic key material, but due to its geno...

Examples

Embodiment 1

[0051] Instrument: Agilent1260 high performance liquid chromatography, 1210 ultraviolet detector

[0052] Chromatographic column: a chromatographic column (150×4.6mm, 5μm) filled with siloxane-bonded silica gel;

[0053] Mobile phase A: triethylamine aqueous solution (adjust pH to 6.2 with phosphoric acid)

[0054] Mobile Phase B: Acetonitrile

[0055] Gradient elution:

[0056] time / min

Mobile phase A / %

Mobile phase B / %

0

85

15

3

85

15

35

45

55

36

85

15

45

85

15

[0057] Flow rate: 1.0ml / min

[0058] Detection wavelength: 210nm

[0059] Column temperature: 30°C

[0060] Injection volume: 10μl

[0061] Diluent: acetonitrile: triethylamine aqueous solution (adjust pH to 10-11 with phosphoric acid) = 40:60 (v / v)

[0062] Run time: 45 minutes

[0063] Experimental steps:

[0064] Need testing solution: take by weighing dexlansoprazole crude drug 1.0014g and put 10mL measuri...

Embodiment 2

[0071] Instrument: Agilent1260 high performance liquid chromatography, 1210 ultraviolet detector

[0072] Chromatographic column: a chromatographic column (150×4.6mm, 5μm) filled with siloxane-bonded silica gel;

[0073] Mobile phase A: triethylamine aqueous solution (adjust pH to 5.5 with phosphoric acid)

[0074] Mobile Phase B: Acetonitrile

[0075] Gradient elution:

[0076] time / min

Mobile phase A / %

Mobile phase B / %

0

85

15

3

85

15

35

45

55

36

85

15

45

85

15

[0077] Flow rate: 1.2ml / min

[0078] Detection wavelength: 210nm

[0079] Column temperature: 30°C

[0080] Injection volume: 10μl

[0081] Diluent: acetonitrile: triethylamine aqueous solution (adjust pH to 10-11 with phosphoric acid) = 40:60 (v / v)

[0082] Run time: 45 minutes

[0083] Experimental steps:

[0084] Cumyl hydroperoxide reference stock solution: use a diluent to prepare a solution with a concen...

Embodiment 3

[0090] Instrument: Agilent1260 high performance liquid chromatography, 1210 ultraviolet detector

[0091] Chromatographic column: a chromatographic column (150×4.6mm, 5μm) filled with siloxane-bonded silica gel;

[0092] Mobile phase A: triethylamine aqueous solution (adjust pH to 7.0 with phosphoric acid)

[0093] Mobile Phase B: Methanol

[0094] Gradient elution:

[0095] time / min

Mobile phase A / %

Mobile phase B / %

0

85

15

3

85

15

35

45

55

36

85

15

45

85

15

[0096] Flow rate: 0.8ml / min

[0097] Detection wavelength: 210nm

[0098] Column temperature: 30°C

[0099] Injection volume: 10μl

[0100] Diluent: acetonitrile: triethylamine aqueous solution (adjust pH to 10-11 with phosphoric acid) = 40:60 (v / v)

[0101] Run time: 45 minutes

[0102] Experimental steps:

[0103] Cumyl hydroperoxide reference stock solution: use a diluent to prepare a solution with a concentrat...

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