Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Rauwolfia alkaloid; treatment of hypertension.
DEFINITION
Methyl 11,17α-dimethoxy-18β-[(3,4,5-trimethoxybenzoyl)oxy]-3β,20α-yohimban-16β-carboxylate.
Content
— reserpine: 98.0 per cent to 102.0 per cent (dried substance),
— total alkaloids: 99.0 per cent to 101.0 per cent (dried substance).
CHARACTERS
Appearance
White or slightly yellow, small crystals or crystalline powder, darkening slowly on exposure to light.
Solubility
Practically insoluble in water, very slightly soluble in ethanol (96 per cent).
IDENTIFICATION
Infrared absorption spectrophotometry (2.2.24).
Comparison reserpine CRS.
TESTS
Specific optical rotation (2.2.7)
-116 to -128 (dried substance).
Dissolve 0.250 g in chloroform R and dilute to 25.0 mL with the same solvent. Examine immediately.
Oxidation products
Dissolve 20 mg in glacial acetic acid R and dilute to 100.0 mL with the same acid. The absorbance (2.2.25) measured immediately at the absorption maximum at 388 nm is not greater than 0.10.
Loss on drying (2.2.32)
Maximum 0.5 per cent, determined on 0.500 g by drying in vacuo at 60 °C at a pressure not exceeding 0.7 kPa for 3 hours.
Sulfated ash (2.4.14)
Maximum 0.1 per cent, determined on 0.5 g.
ASSAY
Total alkaloids
Dissolve 0.500 g in a mixture of 6 mL of acetic anhydride R and 40 mL of anhydrous acetic acid R. Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20).
1 mL of 0.1 M perchloric acid is equivalent to 60.9 mg of total alkaloids.
Reserpine
Protect the solutions from light Moisten 25.0 mg with 2 mL of ethanol (96 per cent) R, add 2 mL of 0.25 M sulfuric acid and 10 mL of ethanol (96 per cent) R, and warm gently to dissolve. Cool and dilute to 100.0 mL with ethanol (96 per cent) R. Dilute 5.0 mL of this solution to 50.0 mL with ethanol (96 per cent) R. Prepare a reference solution in the same manner using 25.0 mg of reserpine CRS. Place 10.0 mL of each solution separately in 2 boiling-tubes, add 2.0 mL of 0.25 M sulfuric acid and 2.0 mL of a freshly prepared 3 g/L solution of sodium nitrite R. Mix and heat in a water-bath at 55 °C for 35 min. Cool, add 1.0 mL of a freshly prepared 50 g/L solution of sulfamic acid R and dilute to 25.0 mL with ethanol (96 per cent) R. Measure the absorbance (2.2.25) of each solution at the absorption maximum at 388 nm, using as the compensation liquid 10.0 mL of the same solution prepared at the same time in the same manner, but omitting the sodium nitrite.
Calculate the content of C33H40N2O9 from the absorbances measured and the concentrations of the solutions.
STORAGE
Protected from light.
