Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Antiepileptic.
DEFINITION
2-Propylpentanoic acid.
Content
99.0 per cent to 101.0 per cent.
CHARACTERS
Appearance
Colourless or very slightly yellow, clear liquid, slightly viscous.
Solubility
Very slightly soluble in water, miscible with ethanol (96 per cent) and with methylene chloride. It dissolves in dilute solutions of alkali hydroxides.
IDENTIFICATION
Infrared absorption spectrophotometry (2.2.24).
Comparison valproic acid CRS.
TESTS
Appearance of solution
The solution is clear (2.2.1) and not more intensely coloured than reference solution Y5 (2.2.2, Method II). Dissolve 2.0 g in dilute sodium hydroxide solution R and dilute to 10 mL with the same alkaline solution.
Related substances
Gas chromatography (2.2.28).
Test solution Dissolve 0.500 g of the substance to be examined in heptane R and dilute to 100.0 mL with the same solvent.
Reference solution (a) Dissolve 5 mg of valproic acid for system suitability CRS (containing impurity K) in 1.0 mL of heptane R.
Reference solution (b) Dilute 1.0 mL of the test solution to 100.0 mL with heptane R. Column:
— material: wide-bore fused silica;
— size: l = 30 m, Ø = 0.53 mm;
— stationary phase: macrogol 20 000 2-nitroterephthalate R (film thickness 0.5 µm).
Carrier gas helium for chromatography R. Flow rate 8 mL/min.
Temperature:
| Time (min) | Temperature (°C) | |
| Column | 0 – 5 | 80 |
| 5 – 15 | 80 → 150 | |
| 15 – 28.3 | 150 → 190 | |
| 28.3 – 30 | 190 | |
| Injection port | 220 | |
| Detector | 220 | |
Detection Flame ionisation.
Injection 1 µL.
Relative retention With reference to valproic acid (retention time = about 17 min): impurity K = about 0.97.
System suitability Reference solution (a):
— resolution: minimum 2.0 between the peaks due to impurity K and valproic acid.
Limits:
— impurity K: not more than 0.15 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.15 per cent);
— unspecified impurities: for each impurity, not more than 0.05 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent);
— total: not more than 0.2 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.2 per cent);
— disregard limit: 0.03 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.03 per cent).
Sulfated ash (2.4.14)
Maximum 0.1 per cent, determined on 1.0 g.
ASSAY
Dissolve 0.100 g in 25 mL of ethanol (96 per cent) R. Add 2 mL of water R. Titrate with 0.1 M sodium hydroxide, determining the end-point potentiometrically (2.2.20).
1 mL of 0.1 M sodium hydroxide is equivalent to 14.42 mg of C8H16O2.
STORAGE
In an airtight container.
IMPURITIES
Specified impurities K.
Other detectable impurities (the following substances would, if present at a sufficient level, be detected by one or other of the tests in the monograph. They are limited by the general acceptance criterion for other/unspecified impurities and/or by the general monograph Substances for pharmaceutical use (2034). It is therefore not necessary to identify these impurities for demonstration of compliance. See also 5.10. Control of impurities in substances for pharmaceutical use) A, B, C, D, E, F, G, H, I, J, L.
A. pentanoic acid (valeric acid),
B. (2RS)-2-ethylpentanoic acid,
C. (2RS)-2-(1-methylethyl)pentanoic acid,
D. 2,2-dipropylpentanoic acid,
E. pentanamide (valeramide),
F. 2-propylpentanamide,
G. 2,2-dipropylpentanamide,
H. pentanenitrile (valeronitrile),
I. 2-propylpentanenitrile,
J. 2,2-dipropylpentanenitrile,
K. (2RS)-2-ethyl-2-methylpentanoic acid,
L. (2RS)-2-methylpentanoic acid.
