Highly-sensitive method for determining residual quantity of piperidine in bulk drug

A technology of raw materials and detection methods, which is applied in the field of high-sensitivity detection, can solve the problems of not meeting the limit requirements and poor sensitivity, and achieve the effects of increased sensitivity, accurate and reliable results, and simple and fast methods

Inactive Publication Date: 2018-03-30
YABAO PHARMA GRP CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Piperidine is very polar and has no ultraviolet absorption. Currently, gas chromatography (FID, NPD detector) is commonly used for detection, but its sensitivity is poor and far below the limit requirements. In order to further control the safety of raw materials, a high-sensitivity A method for the determination of piperidine residues is necessary

Method used

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  • Highly-sensitive method for determining residual quantity of piperidine in bulk drug
  • Highly-sensitive method for determining residual quantity of piperidine in bulk drug
  • Highly-sensitive method for determining residual quantity of piperidine in bulk drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Embodiment 1: the qualitative of piperidine derivative

[0048] Instruments and Conditions:

[0049] Agilent1290 liquid chromatograph, pump model is G4220A, ultraviolet detector model G4212A, electrospray ionization detector model is G6460B and Chemstation processing software, chromatographic column: phenomenonex C18 (250*4.6mm, 5μm), ultraviolet detection wavelength It is 388nm, and the mass spectrum parameters are: Fragment: 135; Cell Accelerator: 7; Positive.

[0050]Mobile phase: acetonitrile-water (65:35, v / v), flow rate 1ml / min, injection volume 10μl.

[0051] Experimental steps:

[0052] Preparation of piperidine reference substance stock solution: Take an appropriate amount of reference substance (AR, batch number: J01010, Beijing Chemical Plant), dissolve it in DMSO, and prepare a piperidine reference substance stock solution with a final concentration of 0.1 mg / ml.

[0053] Preparation of 2,4-dinitrofluorobenzene stock solution: Take an appropriate amount o...

Embodiment 2

[0057] Example 2 Derivatization reaction time investigation

[0058] Instruments and Conditions

[0059] Agilent1260 liquid chromatograph, the model of pump is G1311A, the ultraviolet detector model G1315D, and Chemstation processing software, chromatographic column: phenomenonex C18 (250*4.6mm, 5 μ m), ultraviolet detection wavelength is 388nm, mobile phase: acetonitrile-water ( 65:35, v / v), flow rate 1ml / min, injection volume 10μl.

[0060] experiment procedure:

[0061] Preparation of piperidine reference substance stock solution: Take an appropriate amount of reference substance and dissolve it in DMSO to a final concentration of 0.1 mg / ml.

[0062] Preparation of 2,4-dinitrofluorobenzene stock solution: Take an appropriate amount of sample and dissolve it in DMSO to a final concentration of 4 mg / ml.

[0063] Derivation reaction: Take 1ml of piperidine reference substance, put it into a 100ml volumetric flask, add 1ml of 2,4-dinitrofluorobenzene stock solution precisely...

Embodiment 3

[0066] Embodiment 3: the determination of liquid chromatography condition:

[0067] Analyze according to different liquid chromatography conditions in Table 1

[0068] Table 1:

[0069]

[0070] .

[0071] System sample preparation conditions are shown in Table 2:

[0072] Table 2

[0073]

[0074] see results Figure 4 and Figure 5 .

[0075] Test conclusion: meet the chromatographic conditions of above-mentioned condition 1 and condition 2, piperidine derivatives all can go out peak normally, and retention time changes to some extent, but does not affect normal determination, considers that piperidine derivatives peak shape is best (as peak width minimum, high resolution), the optimum flow rate is 1ml / min, the optimum column temperature is 30°C, and the optimum injection volume is 10μl.

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Abstract

The invention provides a highly-sensitive method for determining the residual quantity of piperidine in a bulk drug. The method comprises the following steps: 1, taking a bulk drug sample, diluting the sample, adding 2,4-dinitrofluorobenzene, adding an acid binding agent, and carrying out a derivation reaction; and 2, determining the residual quantity of piperidine in the sample through liquid chromatography by using an ultraviolet detector. The derivation reaction adopted by the method has mild conditions, can be carried out at room temperature, and is fast and complete; a generated derivation product has ultraviolet absorption, the detection sensitivity is obviously improved, and the detection limit can reach 0.30 ng; and a derivation reaction solution has a good state stability, and thedetermination method is stable and reliable.

Description

technical field [0001] The invention relates to a high-sensitivity detection method for residual piperidine in raw materials. Background technique [0002] Piperidine, also known as hexahydropyridine, is a secondary amine and organic base widely used in organic synthesis, such as as a catalytic reagent in aldol condensation and Michael addition, for regulating sulfoxide-sulfinic acid rearrangement Thiophilic reagents, as well as the constituent units in the synthesis of enamines or imines, etc., play an important role in the fields of scientific research, chemical industry and medicine. Its structural formula is: [0003] [0004] Piperidine has certain toxicity and is the second type of precursor. The 2015 edition of Chinese Pharmacopoeia, USP38<467>Residual Solvents and ICHQ3C have not made clear regulations on the residue limit of piperidine, and the formulation of the limit should refer to its toxicity data according to common sense (http: / / www.basechem.org / ch...

Claims

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Application Information

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IPC IPC(8): G01N30/02G01N30/06
CPCG01N30/02G01N30/06G01N2030/067
Inventor 李赛雷张希玉李琦
Owner YABAO PHARMA GRP CO LTD
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