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Method for separation determination of related substances in bulk drugs and preparations of paricalcitol through HPLC method

A technology of paricalcitol and related substances, applied in the field of analytical chemistry, which can solve the problems of low product specifications, reduced retention time of main peaks, interference detection, etc., and achieve good separation, accurate results, and strong specificity

Active Publication Date: 2016-04-06
CHONGQING HUAPONT PHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] Both the USP37 version of the quality standard for Paricalcitol bulk drug and the USP37 version of the quality standard for Paricalcitol injection use reversed-phase high-performance liquid chromatography to detect related substances. The inventors of the application use these two standards for Paricalcitol injection There are certain limitations in the detection of related substances in riscalcitol capsule preparations. The reasons are: (1) there are many peaks of oily matrix excipients in Paricalcitol soft capsules, and the excipient peaks range from 10 min to 30 min. , the auxiliary material peak is relatively large, which seriously interferes with the detection of related substances in this product; (2) due to the low product specification, after dilution and injection, the impurity detection limit level cannot be met; (3) the reversed-phase liquid chromatography is used to determine related substances , the matrix has a certain solubility for the main peak. After continuous injection, the retention time of the main peak decreases successively. In the gradient elution, the washing time of 100% acetonitrile is extended to 30min, but it cannot completely inhibit
Therefore, there is no quality standard for Paricalcitol Soft Capsules

Method used

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  • Method for separation determination of related substances in bulk drugs and preparations of paricalcitol through HPLC method
  • Method for separation determination of related substances in bulk drugs and preparations of paricalcitol through HPLC method
  • Method for separation determination of related substances in bulk drugs and preparations of paricalcitol through HPLC method

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Experimental program
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Embodiment 1

[0045] The determination of embodiment 1 chromatographic conditions

[0046]Based on the limitations of the determination of related substances in Paricalcitol Soft Capsules by reversed-phase liquid chromatography, as described in the background of the present invention, after repeated screening, a normal-phase chromatography system was finally selected, and a gradient elution method was adopted for Paricalcitol Soft Capsules. Related substances inspection of riscalcidol soft capsules to improve detection sensitivity and reduce peak width expansion caused by large-volume injection; increase column temperature to 45°C to speed up peak elution time of oily matrix; choose to use silica gel column for this product The separation effect of impurity peaks and the peak shape of the main peak were ideal; at the same time, in order to improve the detection ability of impurities, the injection volume was selected as 100 μl. The results of the specificity study showed that the peak of th...

Embodiment 2

[0052] Impurity A is an impurity that may be introduced during the synthesis of the Paricalcitol bulk drug, and its structure is as follows:

[0053]

[0054] Weigh about 20 mg of the paricalcitol reference substance, put it in a 10ml measuring bottle, add absolute ethanol to dissolve and dilute to the mark, and use it as the paricalcitol reference substance stock solution.

[0055] Weigh about 10 mg of the impurity A reference substance (content 95.5%), put it in a 100ml measuring bottle, add absolute ethanol to dissolve and dilute to the mark, shake well, and use it as the impurity A reference substance stock solution.

[0056] Measure the appropriate amount of Paricalcitol reference substance stock solution and impurity A reference substance stock solution respectively, add n-hexane-isopropanol (volume ratio 90:10) to dilute, and prepare to contain about 10.0% of Paricalcitol in every 1ml. μg and impurity A 0.1μg mixed solution, as the system suitability solution.

[00...

Embodiment 3

[0061] The mensuration of embodiment 3 paricalcitol soft capsule

[0062] Get the contents of 10 paricalcitol soft capsules and mix them as the test solution. At the same time, a blank matrix (that is, a blank matrix without the main drug paricalcitol) was taken as a control solution.

[0063] Accurately measure 50 μl each of the test solution and the reference solution respectively, inject it into a liquid chromatograph, measure according to the optimum chromatographic conditions determined in Example 1, and record the chromatogram. The chromatogram of paricalcitol soft capsule need testing solution detection is as follows image 3 as shown, Figure 4 It is the detection chromatogram of the blank matrix control solution. Depend on Figure 4 It can be seen that the blank matrix of Paricalcitol Soft Capsules in the normal phase chromatographic system, due to poor solubility, basically no peaks, and does not interfere with the detection of the main peak of Paricalcitol and i...

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Abstract

The present invention belongs to the field of analytical chemistry, and particularly relates to a method for separation and determination of related substances in bulk drugs and preparations of paricalcitol by using a high-performance liquid chromatography method. According to the method, a normal phase liquid chromatography method is used, the polarity of the stationary phase of the used chromatography column is greater than the polarity of the mobile phase, the peak areas of various substances in a sample solution are determined by using the normal phase liquid chromatography method, and the relative contents of various substances are calculated according to peak area normalization. Compared to the method in the prior art, the method of the present invention has characteristics of strong specificity, good paricalcitol and impurity separation effect and the like, and can be used for impurity detection and quality control during preparation process of paricalcitol bulk drugs and paricalcitol soft capsules.

Description

technical field [0001] The invention belongs to the field of analytical chemistry, and in particular relates to a method for separating and measuring related substances in paricalcitol raw materials and preparations by using high performance liquid chromatography. Background technique [0002] Paricalcitol is an analogue of vitamin D active substance calcitriol, which is used for the prevention and treatment of secondary hyperparathyroidism (SHPT, mainly manifested as elevated PTH). The molecular formula of Paricalcitol is C 27 h 44 o 3 , the chemical name is (7E,22E)-19-desmethyl-9,10-cycloergosta-5,7,22-triene-1α,3β,25-triol, and its structural formula is as follows: [0003] [0004] The injection preparation of Paricalcitol was launched in 1998 and has become the most widely used drug for the prevention and treatment of SHPT in dialysis patients. Paricalcitol 1, 2 and 4mcg capsule formulations are also approved by the FDA for the prevention and treatment of second...

Claims

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Application Information

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IPC IPC(8): G01N30/02
Inventor 管璐晗赵静陈李平
Owner CHONGQING HUAPONT PHARMA
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