Loss on drying 731
Dry it in vacuum, but at a pressure not below 10 mm of mercury, at 60
to constant weight: it loses not more than 0.5% of its weight.
Solution A, Solution B, and Mobile phase
Proceed as directed in the Assay.
Proceed as directed in the Assay. To evaluate the system suitability requirements, use the Resolution solution and the Standard preparation prepared as directed in the Assay.
Dissolve about 20 mg of Guaifenesin in 10 mL of Solution B.
Diluted test solution
Transfer 1.0 mL of the Test solution to a 100-mL volumetric flask, dilute with Solution B to volume, and mix.
Separately inject equal volumes (about 10 µL) of the Test solution
and the Diluted test solution
into the chromatograph, record the chromatograms, and measure the areas for the major peaks. All of the peaks are baseline resolved. Calculate the percentage of each impurity in the portion of Guaifenesin taken by the formula:
F(ri / rS),
in which F
is a response factor equal to 0.63 for the guaiacol peak, having a relative retention time of 1.4, and 1.0 for all other impurities; ri
is the area of each peak, other than that of the main guaifenesin peak, obtained from the Test solution;
is the area of the main peak obtained from the Diluted test solution:
not more than 1.5% of 2-(2-methoxyphenoxy)-1,3-propanediol (guaifenesin
-isomer), the peak for which occurs at a relative retention time of about 0.9, is found; not more than 0.03% of guaiacol is found; not more than 0.5% of any other individual impurity is found; and not more than 1.0% of total impurities, excluding guaifenesin
-isomer and guaiacol, is found.
Prepare a mixture of water and glacial acetic acid (990:10).
Use variable mixtures of Solution A
and Solution B
as directed for Chromatographic system
. Make adjustments if necessary (see System Suitability
under Chromatography 621
Prepare a solution of USP Guaifenesin RS
in Solution B
having a known concentration of about 0.5 mg per mL.
Transfer about 25 mg of Guaifenesin, accurately weighed, to a 50-mL volumetric flask, dissolve in and dilute with Solution B to volume, and mix.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 276-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1 mL per minute. The chromatograph is programmed as follows.
| Solution A
| Solution B
Chromatograph the Resolution solution
, and record the peak responses as directed for Procedure:
the relative retention times are about 0.9 for guaifenesin
-isomer, 1.0 for guaifenesin, and 1.3 for guaiacol; and the resolution, R,
between guaifenesin and guaiacol is not less than 3. Chromatograph the Standard preparation,
and record the peak responses as directed for Procedure:
the relative standard deviation for replicate injections is not more than 1.0%.
Separately inject equal volumes (about 10 µL) of the Standard preparation
and the Assay preparation
into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the quantity of C10
in the portion of Guaifenesin taken by the formula:
50C(rU / rS),
in which C
is the concentration, in mg per mL, of USP Guaifenesin RS
in the Standard preparation;
are the peak areas obtained from the Assay preparation
and the Standard preparation,
respectively. Calculate the percentage of C10
in the portion of Guaifenesin taken. To this value, add the percentage of guaifenesin
-isomer found in the test for Chromatographic purity.