Photodegradation impurities of melphalan and salt thereof and HPLC detection method of melphalan and salt thereof
A detection method, the technology of melphalan, is used in the field of photolysis impurities and HPLC detection, which can solve the problems of inability to monitor PD1 and PD2 at the same time, and inability to accurately quantify, to improve detection sensitivity and durability, and prolong retention time. , Control the effect of product quality
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Embodiment 1
[0039] Example 1: Discovery and Identification of Photodegradation Impurities
[0040] Chromatographic conditions (refer to Pharmacopoeia method): chromatographic column is Waters Atlantis T3 column (4.6mm×150mm, 3μm); mobile phase A is 0.01mol / L ammonium acetate solution (adjust pH to 4.6 with acetic acid), mobile phase B is acetonitrile, gradient The elution is as follows: 0min(95%A-5%B)→20min(40%A-60%B)→25min(40%A-60%B); the flow rate is 1.5ml / min; the injection volume is 10μl; The detection wavelength is 260nm; the column temperature is 35°C.
[0041] Place the melphalan hydrochloride under light conditions (4500lx±500lx) for 10 days, dissolve it with methanol and dilute it to a 0.5mg / ml solution, and inject and analyze according to the above-mentioned chromatographic conditions. From the chromatogram of melphalan hydrochloride illumination sample ( figure 1 ) as can be seen, melphalan hydrochloride can produce two larger degradation impurities under light conditions, wh...
Embodiment 2
[0044] Embodiment 2: the synthesis of 4-(2-chloroethylamino)-L-phenylalanine hydrochloride
[0045] The synthetic route is as follows:
[0046]
[0047]Dissolve 2g of N,N-phthaloyl-4-amino-L-phenylalanine ethyl ester (compound A) in 20ml of ethanol, add 1ml of triethylamine and 0.8g of bromoethanol and react at room temperature for 24 After distilling off ethanol under reduced pressure, a large amount of water was added, extracted with dichloromethane, and the organic phase was collected and separated by column chromatography to obtain 1.7 g of compound B. Dissolve 1.5g of compound B in 15ml of dichloromethane, add 0.8ml of phosphorus oxychloride, react at 30°C for 5 hours, remove the dichloromethane by rotary evaporation, and obtain 1.3g of compound C. Compound C was refluxed with concentrated hydrochloric acid for 12 hours, then stirred in hydrogen chloride ethanol solution at low temperature for 1 hour, and the solvent was removed by rotary evaporation. The residue was...
Embodiment 3
[0049] Embodiment 3: The inventive method is to the mensuration of photodegradation impurity
[0050] 1. Chromatographic conditions
[0051] Chromatographic column: Atlantis HILIC column (4.6mm×150mm, 3μm); mobile phase: 0.1mol / L ammonium formate solution (formic acid to adjust the pH to 3.0): acetonitrile = 13:87; flow rate: 1.0ml / min; injection volume: 20μl; column temperature: 35°C; detection wavelength: 260nm. Under the chromatographic conditions, the photodegradation impurities PD1 and PD2 could be completely separated from other impurities in melphalan hydrochloride.
[0052] 2. Solution Preparation
[0053] Impurity stock solution: Accurately weigh appropriate amounts of impurities PD1 and PD2 respectively, dissolve and dilute with methanol to form an impurity stock solution with a concentration of 25 μg / ml.
[0054] Reference substance solution: take the impurity stock solution and quantitatively dilute it with methanol to a solution of 1.5 μg / ml.
[0055] Test sol...
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