Method for determining content of GS-441524 in preparation of polyethylene glycol and water

Abstract

The invention discloses a method for determining a content of GS-441524 in a preparation of polyethylene glycol and water. The method comprises the following steps: a, preparing a test sample: precisely measuring a test preparation of a remdesivir intermediate, and diluting the test preparation with an acetonitrile / aqueous solution to obtain the test sample; b, preparing a standard solution: precisely weighing a reference substance, dissolving by using the acetonitrile / aqueous solution, and quantitatively diluting step by step to form a series of standard solutions; and c, determining by usinga liquid chromatography-mass spectrometry method: quantitatively measuring the series of standard solutions in the step b, determining by using the liquid chromatography-mass spectrometry method, andcalculating a standard curve by using a peak area in an extraction ion flow diagram of GS-441524; quantitatively measuring the test sample in the step a, and carrying out liquid chromatography-mass spectrometry determination; avoiding a double-peak phenomenon of the sample; and making the GS-441524 and the molecules of the polyethylene glycol have a good separation degree, wherein a mass spectrumdetection limit is superior to 0.05 mug / mL, and a quantification limit is superior to 0.1 mug / mL.

Description

technical field [0001] The invention relates to the field of pharmaceutical analysis, in particular to a method for determining the content of remdesivir intermediate GS-441524 in preparations made of polyethylene glycol and water as solvents. Background technique [0002] Remdesivir intermediate GS-441524 is a small molecule nucleotide analog and is a precursor molecule for the synthesis of pharmacologically active nucleoside triphosphates; GS-441524 can also be called nucleoside triphosphate competitive Inhibitors that exhibit potent antiviral activity against many RNA viruses. [0003] CAS registration number of GS-441524: 1191237-69-0, molecular formula: C12H13N5O4 molecular weight: 291.267; systematic chemical name (2R, 3R, 4S, 5R)-2-(4-aminopyrrolo[2,1-f] [1,2,4]triazin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-carbonitrile; the English chemical name is (2R,3R,4S,5R)- 2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrof...

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Problems solved by technology

[0004] GS-441524 itself has been reported in the literature, and it has a strong inhibitory effect on feline infectious peritonitis (FIP) virus, and the half-maximal effect concentration (EC 50 ) is 0.78 μM; Pharmacologically, GS-441524 acts as an alternative substrate for viral RNA polymerase, causing the termination of viral RNA chain polymerization; whether as a synthetic intermediate or metabolite of remdesivir, or directly as a drug itself, In the field of drug analysis, the content of GS-441524 is required to be accurately determined; at present, domestic and foreign literature has not yet seen relevant reports on the content determination method of remdesivir intermediate GS-441524 in the preparation system of polyethylene glycol and water as solvents

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