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(November 2019)
DRAFT FOR COMMENTS
Please send any comments you may have on this draft working document to Dr Herbert Schmidt, Technical Officer, Medicines Quality Assurance, Technologies Standards and Norms (email: [email protected]) by 15 February 2020.
Working documents are sent out electronically and they will also be placed on the Medicines website for comments under "Current projects".
http://www.who.int/medicines/areas/quality_safety/quality_assurance/guidelines/en
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Molecular formula. C22H29FV3O9P
Relative molecular mass. 529.5
Graphic formula.
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Chemical name. Propan-2-yl V-[(5j-{[(2R ,3R ,4R ,5R )-5-(2,4-dioxo-3,4-dihydropyrimidin1(2H)-yl)-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy}phenoxyphosphoryl]-L-alaninate; CAS Reg. Vo. 1190307-88-0.
Description. A white to off-white powder.
Solubility. Slightly soluble in water R, freely soluble in dehydrated ethanol R and acetone R, soluble in 2-propanol R and insoluble in heptane R.
Category. Antiviral (Hepatitis C viral polymerase nucleotide inhibitor)
Storage. Sofosbuvir should be kept in a well-closed container and stored at a temperature below 30 °C.
Additional information. Sofosbuvir may exhibit polymorphism.
Definition. Sofosbuvir contains not less than 97.5 % and not more than 102.0 % of C22H29FN3O9P with reference to the anhydrous substance.
Identity tests
* Either test A alone or tests B and C may be applied:
A. Carry out the examination as described under 1.7 Spectrophotometry in the infrared region. The infrared absorption spectrum is concordant with the spectrum obtained from sofosbuvir RS or with the reference spectrum of sofosbuvir.
If the spectra thus obtained are not concordant repeat the test using the residues obtained by separately dissolving the test substance and sofosbuvir RS in a small amount of methanol R and evaporating to dryness. The infrared absorption spectrum is concordant with the spectrum obtained from sofosbuvir RS.
B. Carry out the test as described under 114.4 High-performance liquid chromatography using the conditions given under "Assay". The retention time of the principal peak in the chromatogram obtained with solution (1) corresponds to the retention time of the peak due to sofosbuvir in the chromatogram obtained with solution (2).
C. Carry out the test as described under 1.14.1 Thin-layer chromatography, using silica gel R24 as the coating substance and a mixture of 6 volumes of dichloromethane R, 1 volume of methanol R, 4 volumes of ethyl acetate R...