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A platinum-containing compound, its preparation method, separation method and application

A technology for platinum compounds and separation methods, which is applied in platinum-based organic compounds, platinum-group organic compounds, chemical instruments and methods, etc., and can solve problems such as few studies, inability to identify, confirm structures, and lack of related substances.

Active Publication Date: 2021-08-13
SHANGHAI INST OF PHARMA IND CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The problem to be solved by the present invention is to overcome the shortcomings of nedaplatin-related substances in this field, the lack of preparation and separation methods, and the inability to identify and confirm the structure of the related substances, and then provide a platinum-containing Compounds, methods for their preparation, methods of isolation and applications

Method used

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  • A platinum-containing compound, its preparation method, separation method and application
  • A platinum-containing compound, its preparation method, separation method and application
  • A platinum-containing compound, its preparation method, separation method and application

Examples

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Embodiment 1

[0049] Embodiment 1 Production of platinum-containing compounds as shown in formula 1

[0050] This example investigates the generation of the platinum-containing compound shown in Formula 1 after nedaplatin is placed for a period of time.

[0051] The instrument used in this embodiment is:

[0052] 2695 high performance liquid chromatography-mass spectrometry system [equipped with ultraviolet detector, ESI source and MassLynx 4.1 data processing system] (Waters Company).

[0053] In the present embodiment, HPLC analysis condition is:

[0054] The chromatographic column is TSK GEL AMIDE-HR80(5) hydrophilic chromatographic column (4.6×250mm, 5μm); the mobile phase is 0.1% n-hexylamine (adjusted to pH5.50 with formic acid)-acetonitrile (30:70); the detection wavelength is 220nm; The flow rate is 1ml / min; the column temperature is 30°C.

[0055] Mass spectrometry conditions: electrospray ionization source, positive ion detection.

[0056] Method A: Accurately weigh about 2 mg o...

Embodiment 4

[0082] In Example 4, the effluent with a retention time of 9.5-12 min was collected, and the solvent was removed by rotary evaporation to obtain a platinum-containing compound standard.

[0083] In Example 2-4, the concentration of the hydrogen peroxide aqueous solution is mass percent concentration.

[0084] In Examples 2-4, see Table 3 for the oxidative degradation conditions of nedaplatin and the obtained HPLC spectra of the corresponding platinum-containing compounds.

[0085] table 3

[0086]

[0087] Combining Table 3 and Figure 8-10 As can be seen, Figure 8 The peak at 11.47min is the nedaplatin peak, and the peak at 22.07min is the platinum-containing compound; Figure 9 The peak at 6.67min is the nedaplatin peak, and the peak at 9.64min is the platinum-containing compound; and Figure 10 Due to the prolongation of oxidative degradation time, nedaplatin is almost completely degraded, thus producing the impurity peak at 3.54min, while the peak eluting time of t...

Embodiment 5

[0089] Purity analysis and mass spectrometry of embodiment 5 platinum-containing compound

[0090] The reagents used in this embodiment are as follows:

[0091] Acetonitrile is chromatographically pure (J.T.Baker Company); deuterated methanol is a product of Cambridge Isotope Laboratories; mobile phase water is commercially available Wahaha purified water (filtered through a 0.22 μm filter membrane).

[0092] The instrument used in this embodiment is as follows:

[0093] 2695 type high performance liquid chromatography-mass spectrometry system [equipped with ultraviolet detector, ESI source and MassLynx 4.1 data processing system] (Waters company);

[0094] Waters Xevo G2-XS QTof high resolution mass spectrometer (Waters company);

[0095] Varian 500M nuclear magnetic resonance instrument;

[0096] Mettler AE-163 electronic balance.

[0097] The standard substance of the platinum-containing compound used in this example was prepared in Example 4 of the present invention. ...

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Abstract

The invention discloses a platinum-containing compound shown in formula 1. The preparation method of the platinum-containing compound comprises the following steps: oxidizing and degrading nedaplatin and hydrogen peroxide in water. The present invention also provides a method for separating the nedaplatin degradation product containing the platinum-containing compound shown in Formula 1, the separation method comprising the following steps: the nedaplatin containing the platinum-containing compound shown in Formula 1 Degradation products can be eluted in the column. The platinum-containing compound shown in formula 1 of the present invention can be used as a reference substance of related substances in the quality control of nedaplatin or its salt, thereby providing a powerful tool for the research of related substances of nedaplatin.

Description

technical field [0001] The invention relates to a platinum-containing compound, its preparation method, separation method and application. Background technique [0002] Nedaplatin belongs to broad-spectrum anticancer drugs, and is a new generation of platinum anticancer drugs with good curative effect and few side effects. Its mechanism of action is the same as that of cisplatin, which binds to the DNA bases of tumor cells and hinders DNA replication to exert its anti-tumor effect. The molecular formula of nedaplatin is C 2 h 8 N 2 o 3 Pt, with a relative molecular weight of 303.17, has the following structure: [0003] [0004] However, since nedaplatin was successfully developed in the 1980s, there have been few studies on its related substances, and the research on related substances is related to the stability, quality research and drug safety of nedaplatin raw materials; therefore, this paper There is an urgent need to study substances related to nedaplatin in ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07F15/00G01N1/28
CPCC07F15/0093G01N1/28
Inventor 李悦还传静陆静蔡鹏俊陈泽
Owner SHANGHAI INST OF PHARMA IND CO LTD
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