Tirofiban degradation impurity, preparation method and application thereof
A technology of tirofiban, quality control method, applied in the field of degrading impurities of tirofiban and its preparation, capable of solving problems such as injury, insufficiency, toxic and side effects
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[0059] According to a specific embodiment of the present invention, high performance liquid chromatography detection condition is as follows:
[0060]
[0061]
[0062] The compound structure shown in formula I is as follows:
[0063]
[0064] According to a specific embodiment of the present invention, before using the high performance liquid chromatography for separation, the solution containing the compound represented by formula I is treated as follows:
[0065] adjusting the pH value of the solution containing the compound represented by formula I to 6-8, and performing extraction treatment with ethyl acetate to obtain an ethyl acetate layer and an aqueous layer;
[0066] Concentrating the ethyl acetate layer to obtain a concentrate, dissolving the concentrate with an aqueous acetonitrile solution to obtain a sample solution;
[0067] The sample solution and the water layer were separated by high performance liquid chromatography, and fractions containing the co...
Embodiment 1
[0074] The acquisition of embodiment 1 impurity
[0075] Preparation of degradation solution: Weigh about 250 mg of tirofiban hydrochloride sample (crude drug, produced by Wuhan Wuyao), put it in a 1-liter volumetric flask, add water to dissolve it completely, dilute to the mark, and shake well. Take 5ml of this solution and place it in a 20ml headspace bottle, add 5ml of 2M HCl solution, shake well, and seal it with a press cap. In this manner, 1 L of the prepared solution was dispensed into 200 20 ml headspace vials. Place the headspace bottle in an oven at 90°C for 4 hours, take it out, and let it cool to room temperature. All solutions were then transferred to 2 L containers as preparative degradation solutions. The degradation solution is divided into two parts, which are processed in the following ways (1) and (2) respectively:
[0076] (1) Part of the above degradation solution is rotary evaporated under reduced pressure to remove part of the water and hydrochloric a...
Embodiment 2
[0084] Embodiment 2 Identification of impurity structure
[0085] Combined with HPLC, HRMS, NMR, the structure identification of the impurity obtained in Example 1 was carried out.
[0086] The HPLC detection conditions are as follows in Table 3:
[0087] table 3
[0088]
[0089] attached figure 1 The HPLC detection results are shown, and the results show that under the degradation conditions of Example 1, two degradation impurities MS475 (3-chloro-tirofiban) and MS262 are produced, and the retention times are 27.1min and 26.6min respectively. It can be seen that tirofiban and 3-chloro-tirofiban can be effectively separated by adopting this method.
[0090] The structure of the impurity was identified by HRMS and NMR.
[0091] HRMS test conditions are shown in Table 4:
[0092] Table 4
[0093]
[0094]
[0095] figure 2 The HRMS detection results are shown, and the results show that the molecular weight of the impurity under high-resolution mass spectrometr...
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