Fexofenadine Hydrochloride
(fex'' oh fen' a deen hye'' droe klor' ide).
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538.12 Benzeneacetic acid, 4-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-
,-dimethyl-, hydrochloride, (±)-.
(±)-p-[1-Hydroxy-4-[4-(hydroxydiphenylmethyl)piperidino]butyl]-
-methylhydratropic acid, hydrochloride
[138452-21-8].» Fexofenadine Hydrochloride contains not less than 98.0 percent and not more than 102.0 percent of C32H39NO4·HCl, calculated on the anhydrous basis.
Packaging and storage—
Preserve in well-closed, light-resistant containers, and store at controlled room temperature.
Labeling—
Where it is the hydrate form, the label so indicates.
USP Reference standards 
11
—
11—
USP Fexofenadine Hydrochloride RS 
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USP Fexofenadine Related Compound A RS
Benzeneacetic acid, 4-[1-oxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-,-dimethyl.
C32H37NO4 499.65
Benzeneacetic acid, 4-[1-oxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-
,-dimethyl.
C32H37NO4 499.65
USP Fexofenadine Related Compound B RS
3-[1-Hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-,-dimethyl benzeneacetic acid hydrochloride.
C32H39NO4·HCl 538.12
3-[1-Hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-
,-dimethyl benzeneacetic acid hydrochloride.
C32H39NO4·HCl 538.12
Identification—
B:
The retention time of the fexofenadine peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
C:
Examine the precipitate formed in the Content of chloride test: a white precipitate is observed.
Water, Method Ic 921:
not more than 2.0% for the anhydrous form; between 6.0% and 10.0% for the hydrate form. [note—“Hydrate” refers to a mixture of dihydrate and trihydrate forms of fexofenadine hydrochloride. ]
921:
not more than 2.0% for the anhydrous form; between 6.0% and 10.0% for the hydrate form. [note—“Hydrate” refers to a mixture of dihydrate and trihydrate forms of fexofenadine hydrochloride. ]
Residue on ignition 281:
not more than 0.1%.
281:
not more than 0.1%.
Heavy metals, Method II 231:
0.002%.
231:
0.002%.
Limit of fexofenadine related compound B—
Ammonium acetate buffer solution—
Add 2.3 mL of glacial acetic acid to 2000 mL of water. Adjust with 6 N ammonium hydroxide to a pH of 4.0 ± 0.1.
Mobile phase—
Prepare a filtered and degassed mixture of Ammonium acetate buffer solution and acetonitrile (80 : 20). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
System suitability solution—
Add about 1.2 mg of USP Fexofenadine Related Compound B RS, accurately weighed, to a 5-mL volumetric flask. Dilute with Mobile phase to volume, and mix. Transfer 2.0 mL of the solution so obtained into a 100-mL volumetric flask; add about 25 mg of USP Fexofenadine Hydrochloride RS, accurately weighed; dilute with Mobile phase to volume; and mix.
Standard solution—
Dilute the System suitability solution quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 2.5 µg of USP Fexofenadine Hydrochloride RS per mL.
Test solution—
Dissolve an accurately weighed quantity of Fexofenadine Hydrochloride in Mobile phase to obtain a solution having a concentration of about 0.25 mg per mL.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm × 25-cm column that contains packing L45. The column is maintained at room temperature. The flow rate is about 0.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.7 for fexofenadine related compound B and 1.0 for fexofenadine; and the resolution, R, between fexofenadine and fexofenadine related compound B is not less than 3.0.
621)—
The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm × 25-cm column that contains packing L45. The column is maintained at room temperature. The flow rate is about 0.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.7 for fexofenadine related compound B and 1.0 for fexofenadine; and the resolution, R, between fexofenadine and fexofenadine related compound B is not less than 3.0.
Procedure—
Separately inject equal volumes (about 20 µL) of the Test solution and the Standard solution into the chromatograph, record the chromatograms, and measure the peak areas. Calculate the percentage of fexofenadine related compound B in the portion of Fexofenadine Hydrochloride taken by the formula:
100/0.8(CS / CT)(rU / rS)
in which 0.8 is the relative response factor for fexofenadine related compound B relative to fexofenadine; CS is the concentration, in mg per mL, of USP Fexofenadine Hydrochloride RS in the Standard solution; CT is the concentration, in mg per mL, of fexofenadine in the Test solution; rU is the peak response for fexofenadine related compound B obtained from the Test solution; and rS is the peak response for fexofenadine obtained from the Standard solution: not more than 0.2% is found.
Related compounds—
Phosphate–perchlorate buffer, Diluting solution, Mobile phase, and Chromatographic system—
Prepare as directed in the Assay.
Standard solution—
Use the Standard preparation, prepared as directed in the Assay.
Reference solution—
Use the Assay preparation, prepared as directed in the Assay.
Test solution—
Use the Assay stock preparation, prepared as directed in the Assay.
Procedure—
Separately inject equal volumes (about 20 µL) of the Test solution, the Standard solution, the Reference solution, and Mobile phase (used as the blank) into the chromatograph; record the chromatograms; and measure the peak areas, excluding the peaks corresponding to those obtained from the Mobile phase. Calculate the percentage of fexofenadine related compound A in the portion of Fexofenadine Hydrochloride taken by the formula:
100(CS /CT)(rU /rS)
in which CS is the concentration, in mg per mL, of USP Fexofenadine Related Compound A RS in the Standard solution; CT is the concentration, in mg per mL, of fexofenadine in the Test solution; and rU and rS are the peak responses for fexofenadine related compound A obtained from the Test solution and the Standard solution, respectively. Calculate the percentage of decarboxylated degradant [(±)-4-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl]-isopropylbenzene], with a relative retention time of 3.2, in the portion of Fexofenadine Hydrochloride taken by the formula:
(100/1.1)(CS /CT)(rU / rS)
in which CS is the concentration, in mg per mL, of USP Fexofenadine Hydrochloride RS in the Standard solution; CT is the concentration, in mg per mL, of fexofenadine in the Test solution; rU is the peak response of the decarboxylated degradant obtained from the Test solution; rS is the peak response of fexofenadine obtained from the Standard solution; and 1.1 is the response factor for the decarboxylated degradant relative to fexofenadine. Calculate the percentage of other impurities in the portion of Fexofenadine Hydrochloride taken by the formula:
100(CS /CT)(ri / rS)
in which CS is the concentration, in mg per mL, of fexofenadine in the Reference solution; CT is the concentration, in mg per mL, of fexofenadine in the Test solution; ri is the peak response for any other impurity obtained from the Test solution; and rS is the peak response of fexofenadine obtained from the Reference solution: not more than 0.2% of fexofenadine related compound A is found, not more than 0.15% of decarboxylated degradant is found, not more than 0.1% of any other unknown impurity is found, and not more than 0.5% of total impurities is found.
Content of chloride—
Dissolve about 300 mg of Fexofenadine Hydrochloride, accurately weighed, in 50 mL of methanol. Titrate with 0.1 N silver nitrate VS, and determine the endpoint potentiometrically (see Titrimetry 541). Each mL of 0.1 N silver nitrate VS is equivalent to 3.545 mg of chloride: not less than 6.45% and not more than 6.75% of chloride is found, calculated on an anhydrous basis.
541). Each mL of 0.1 N silver nitrate VS is equivalent to 3.545 mg of chloride: not less than 6.45% and not more than 6.75% of chloride is found, calculated on an anhydrous basis.
Assay—
Phosphate–perchlorate buffer—
Dissolve 6.64 g of monobasic sodium phosphate and 0.84 g of sodium perchlorate in 1000 mL of water. Adjust with phosphoric acid to a pH of 2.0.
Diluting solution—
Prepare a mixture of acetonitrile and Phosphate–perchlorate buffer (50:50).
Mobile phase—
Prepare a filtered and degassed mixture of Phosphate–perchlorate buffer and acetonitrile (65:35). Add 3 mL of triethylamine per L, and mix. Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Standard preparation—
Prepare a solution of USP Fexofenadine Hydrochloride RS and USP Fexofenadine Related Compound A RS in Mobile phase having known concentrations of about 0.06 mg per mL and 0.005 mg per mL, respectively.
Assay stock preparation—
Transfer about 50 mg of Fexofenadine Hydrochloride, accurately weighed, to a 50-mL volumetric flask, and dissolve in and dilute with Diluting solution to volume to obtain a solution having a concentration of about 1.0 mg of fexofenadine hydrochloride per mL.
Assay preparation—
Transfer 3.0 mL of Assay stock preparation to a 50-mL volumetric flask, and dilute with Mobile phase to volume to obtain a solution having a concentration of about 0.06 mg per mL.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm × 25-cm column that contains packing L11. The column is maintained at room temperature. The flow rate is about 1.5 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the resolution, R, between fexofenadine and fexofenadine related compound A is not less than 10; the tailing factor is not more than 2.0; and the relative standard deviations for replicate injections determined from fexofenadine and fexofenadine related compound A are not more than 2.0% and 3.0%, respectively.
621)—
The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm × 25-cm column that contains packing L11. The column is maintained at room temperature. The flow rate is about 1.5 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the resolution, R, between fexofenadine and fexofenadine related compound A is not less than 10; the tailing factor is not more than 2.0; and the relative standard deviations for replicate injections determined from fexofenadine and fexofenadine related compound A are not more than 2.0% and 3.0%, respectively.
Procedure—
Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, in mg, of C32H39NO4·HCl in the portion of Fexofenadine Hydrochloride taken by the formula:
833.3C(rU / rS)
in which C is the concentration, in mg per mL, of USP Fexofenadine Hydrochloride RS in the Standard preparation; and rU and rS are the peak responses for fexofenadine obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Domenick Vicchio, Ph.D.
Senior Scientific Liaison 1-301-998-6828 |
(SM42010) Monographs - Small Molecules 4 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3186
Pharmacopeial Forum: Volume No. 34(3) Page 606