Chromatographic purity—
pH 4.5 Buffer solution—
Dissolve 6.8 g of monobasic potassium phosphate in 1000 mL of water. Adjust with 18 N phosphoric acid or 10 N potassium hydroxide to a pH of 4.5 ± .05.
Mobile phase—
Prepare a suitably filtered and degassed solution of pH 4.5 Buffer solution and methanol (about 75:25) (see System suitability).
Guaifenesin solution—
Transfer 20.0 mg of
USP Guaifenesin RS to a 50-mL volumetric flask. Dissolve in and dilute with methanol to volume, and mix.
Standard solution—
Transfer 20.0 mg of
USP Methocarbamol RS, accurately weighed, to a 10-mL volumetric flask. Add 1.0 mL of
Guaifenesin solution and 2.0 mL of methanol to dissolve the methocarbamol. Dilute with
pH 4.5 Buffer solution to volume, and mix. Use this solution within 24 hours.
Test solution—
Transfer about 100 mg of Methocarbamol, accurately weighed, to a 50-mL volumetric flask, add 13 mL of methanol to dissolve, dilute with pH 4.5 Buffer solution to volume, and mix. Use this solution within 24 hours.
Chromatographic system
(see
Chromatography 
621
)—The liquid chromatograph is equipped with a 274-nm detector and a 4-mm × 25-cm column that contains packing L1. Adjust the operating conditions so that
System suitability requirements are met.
System suitability—
Chromatograph three replicate 20-µL portions of the Standard solution as directed for the Test solution under Procedure. The analytical system is suitable for use if the peak area percentage of guaifenesin is 2.4 ± 1.0, the relative standard deviation for the peak area percentage is not greater than 4.0%, and the resolution, R, between guaifenesin and methocarbamol is not less than 2.0.
Procedure—
By means of a suitable microsyringe or sampling valve, inject about 20 µL of the
Test solution into the chromatograph. Determine the peak areas of the methocarbamol peak and all extraneous peaks having a retention time greater than 0.5 of the retention time of methocarbamol. The relative retention times are about 0.8 for guaifenesin and 1.0 for methocarbamol. Calculate the percentage of related impurities taken by the formula:
100(2.4 / G)(PE / PT),
in which
G is the area percentage of the guaifenesin peak in the chromatogram of the
Standard solution determined under
System suitability;
PE is the peak area of all extraneous peaks; and
PT is the total of the peak areas of all extraneous peaks and the methocarbamol. The limit is 2.0%.
Assay—
Transfer about 100 mg of Methocarbamol, accurately weighed, to a 100-mL volumetric flask, add methanol to volume, and mix. Transfer 4.0 mL of this solution to a second 100-mL volumetric flask, dilute with methanol to volume, and mix. Concomitantly determine the absorbances of this solution and a Standard solution of
USP Methocarbamol RS in methanol having a known concentration of about 40 µg per mL at the wavelength of maximum absorbance at about 274 nm in 1-cm cells, using methanol as the blank. Calculate the quantity, in mg, of C
11H
15NO
5 in the portion of Methocarbamol taken by the formula:
2.5C(AU / AS),
in which
C is the concentration, in µg per mL, of
USP Methocarbamol RS in the Standard solution; and
AU and
AS are the absorbances of the
Assay solution and the
Standard solution, respectively.
;)
for 2 hours: it loses not more than 0.5% of its weight.