Method for analyzing and detecting polyethylene glycol 200 in vortioxetine

Abstract

The invention relates to a method for detecting polyethylene glycol 200 in vortioxetine, in particular to a method for detecting polyethylene glycol 200 in vortioxetine, which aims at solving the problems that the conventional method for detecting the content of polyethylene glycol 200 adopts an acid-base titration method, and the acid-base titration method is complicated in operation and is easily influenced by laboratory environment. A chromatographic column is a silica gel bonded octadecylsilane column, a differential detector is used, an organic solvent is used as a mobile phase, and an isocratic elution mode is adopted for separation and detection. The method for detecting the polyethylene glycol 200 in the vortioxetine is good in separation degree, high in specificity, high in precision and good in repeatability, and meets methodological research on determination of the polyethylene glycol 200 in the vortioxetine.

Description

Technical Field

[0001] The invention relates to the technical field of chemical medicine and food analysis, and in particular to an analytical detection method for determining polyethylene glycol 200 by liquid chromatography. Compared with acid-base titration, the analytical detection method and application can be significantly improved, and the method has good stability. Background Art

[0002] Major depressive disorder (MDD) is a common disabling disease with a high incidence of non-recovery and relapse, leading to a large number of deaths and morbidity. Only a small number of MDD patients (30-40%) achieve symptom relief after adequate treatment with first-line antidepressants, and many patients fail to reach their pre-illness psychosocial function level. The onset of depression often accompanies a person's life, causing great pain to the individual and family. Current research data show that vortioxetine has definite efficacy and few side effects, and is expected to become the most successful new antidepressant drug.

[0003] Vortioxetine, whose molecular formula is C 18 H 22 N2S, molecular weight is 298.45:

[0004] The structural formula of vortioxetine is:

[0005] In the process of synthesizing vortioxetine, quality analysis is crucial to the purity control of vortioxetine, and a polyethylene glycol 200 analysis and detection method in vortioxetine can guide and detect the synthesis and preparation of vortioxetine, improve the yield and purity of the final product, and thus has important practical significance in the quality control of the vortioxetine synthesis process. Summary of the invention

[0006] The invention provides a method for detecting polyethylene glycol 200 in vortioxetine, thereby being able to quickly, effectively and accurately monitor the purity of vortioxetine and achieve quality control of the final product raw material drug thereof.

[0007] The invention provides a method for analyzing and detecting polyethylene glycol 200 in vortioxetine, which adopts a high performance liquid chromatography method, uses a chromatographic column as a silica gel bonded octadecylsilane column, uses a pure organic solvent as a mobile phase, and performs isocratic elution.

[0008] The isocratic elution program is:

[0009] Preferably, the organic phase is pure methanol.

[0010] Preferably, the chromatographic column provided is YMC-Triart-C18 (4.6 mm×250 mm, 5 µm).

[0011] The analytical determination method of the present invention can be tested according to the following method: Example 1

[0012] 1) Take an appropriate amount of vortioxetine sample, add diluent (methanol) to dissolve and prepare a sample solution containing 5 mg of vortioxetine per 1 ml; 2) Take an appropriate amount of polyethylene glycol 200, add diluent (methanol) to dissolve and prepare a solution containing 5 μg of polyethylene glycol 200 per 1 ml; 3) The optimal flow rate of the mobile phase is 1.0 mL / min, the differential detector, the detection cell temperature is 40°C, the column oven temperature is optimally 40°C, and the injection volume is 20 μl; 4) Elution method: isocratic elution; 5) High performance liquid chromatography: LC-20AT; 6) Accurately measure 20 μl of the above solutions 1 and 2) and inject them into the liquid chromatograph respectively, and record the chromatograms. Example 2

[0013] 1) Take an appropriate amount of vortioxetine sample, add diluent (methanol) to dissolve and prepare a sample solution containing 5 mg of vortioxetine per 1 ml; 2) Take an appropriate amount of polyethylene glycol 200, add diluent (methanol) to dissolve and prepare a solution containing 5 μg of polyethylene glycol 200 per 1 ml; 3) The optimal flow rate of the mobile phase is 1.0 mL / min, the differential detector, the detection cell temperature is 40°C, the column oven temperature is optimally 40°C, and the injection volume is 20 μl; 4) Chromatographic column: YMC-Pack-ODS-AQ (4.6mm×250mm, 5µm); 5) Elution method: isocratic elution; 6) High performance liquid chromatograph: LC-20AT; 7) Accurately measure 20 μl of the above solutions 1 and 2) and inject them into the liquid chromatograph respectively, and record the chromatograms.

[0014] The present invention adopts chromatographic conditions such as a hydrophobic YMC-Pack-ODS-AQ chromatographic column, methanol as an organic phase, and a differential detector, and can effectively completely separate vortioxetine and polyethylene glycol 200. The present invention solves the problem of separation and determination of vortioxetine and polyethylene glycol 200, thereby reducing the occurrence of side reactions, improving the yield and purity of the product, and ensuring that the quality of vortioxetine is controllable. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 This is the HPLC chart of Example 1.

[0016] Figure 2 This is the HPLC chart of vortioxetine and polyethylene glycol 200 in Example 2. DETAILED DESCRIPTION The following examples are used to further understand the present invention, but are not intended to limit the scope of this embodiment.

[0018] Example Instruments and conditions High performance liquid chromatograph: LC-20AT Chromatographic column: YMC-Pack-ODS-AQ (4.6 mm × 250 mm, 5 µm); Mobile phase A: methanol; Pool temperature: 40°C; Column oven temperature: 40°C; Injection volume: 20 μl; Detector: differential detector; Elution method: isocratic elution Take appropriate amounts of vortioxetine and polyethylene glycol 200, dissolve the sample in methanol, and prepare a sample solution containing 5 mg / mL vortioxetine and about 5 µg / mL polyethylene glycol 200. Perform HPLC analysis under the above conditions and record the chromatogram. Figure 2 The chromatographic peak with a retention time of 7.500 min is polyethylene glycol 200, the chromatographic peak with a retention time of 9.000 min is the blank solution peak, and the chromatographic peak with a retention time of 12.500 min is the sample solution peak.

[0019] from Figure 2 It is shown that the method of the present invention can completely separate vortioxetine and polyethylene glycol 200, and can accurately perform quantitative detection, thereby effectively controlling the product quality of vortioxetine.

Claims

1. A method for analyzing and detecting polyethylene glycol 200 in vortioxetine, using high performance liquid chromatography, a chromatographic column is a silica gel bonded octadecylsilane column, a differential detector, an organic solvent as a mobile phase, and isocratic elution, which can completely separate the sample and polyethylene glycol 200.

2. The analytical detection method according to claim 1, wherein the organic phase is selected from acetonitrile or methanol.

3. According to the analytical detection method described in claim 1, polyethylene glycol 200 has no absorption wavelength at 190-400nm in the ultraviolet detector, so it is selected from the differential detector.

4. The analytical detection method according to claim 1, wherein the elution gradient process is:

5. According to the analytical detection method of claim 1, the chromatographic column preferably has a length of 250 mm, a diameter of 4.6 mm, and a filler particle size of 5 µm.

6. According to the analytical detection method according to claim 2, the mobile phase is preferably pure methanol.

7. The analytical detection method according to claims 1 and 3, comprising the following steps: ① setting the flow rate to 0.4~1.5ml / min; ② setting the detection cell temperature to 30-80℃; ③ setting the chromatographic column temperature to 30~80℃; ④ setting the injection volume to 5~20µl.

8. According to the analytical detection method described in claim 7, the chromatographic conditions are optimized as follows: ① the flow rate is preferably 1.0 ml / min; ② the pool temperature is 40°C; ③ the column temperature is preferably 40°C; ④ the injection volume is preferably 10 µl.

9. The analysis and detection method according to claim 3, wherein the structural formula of polyethylene glycol 200 is:

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