Fexofenadine Hydrochloride

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

C₃₂H₃₉NO₄ · HCl 538.12

Benzeneacetic acid, 4-[1-hydroxy-4-[4-(hydroxy diphenylmethyl)-1-piperidinyl]butyl]-α,α-dimethyl-, hydrochloride, (±)-; (±)-p-[1-Hydroxy-4-[4-(hydroxydiphenylmethyl)piperidino]butyl]-α-methylhydratropic acid, hydrochloride CAS RN®: 153439-40-8; UNII: 2S068B75ZU.

1 DEFINITION

Fexofenadine Hydrochloride contains NLT 98.0% and NMT 102.0% of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl), calculated on the anhydrous basis.

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

B. The retention time of the fexofenadine peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

C.

Analysis: Examine the precipitate formed in Other Components for the Content of Chloride test.

Acceptance criteria: A white precipitate is observed.

3 ASSAY

3.1 Procedure

Buffer: 6.64 g/L of monobasic sodium phosphate and 0.84 g/L of sodium perchlorate in water. Adjust with phosphoric acid to a pH of 2.0.

Diluent: Acetonitrile and Buffer (1:1)

Mobile phase: Acetonitrile and Buffer (7:13). Add 3 mL/L of triethylamine.

Standard solution: 0.06 mg/mL of USP Fexofenadine Hydrochloride RS and 0.005 mg/mL of USP Fexofenadine Related Compound A RS in

3.2 Mobile phase

Sample stock solution: 1.0 mg/mL of Fexofenadine Hydrochloride in Diluent

Sample solution: 0.06 mg/mL of Fexofenadine Hydrochloride in Mobile phase from the Sample stock solution

3.3 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 25-cm; packing L11

Flow rate: 1.5 mL/min

Injection volume: 20 μL

3.4 System suitability

Sample: Standard solution

3.5 Suitability requirements

Resolution: NLT 10 between fexofenadine and fexofenadine related compound A

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0% for fexofenadine and NMT 3.0% for fexofenadine related compound A

3.6 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl) in the portion of Fexofenadine Hydrochloride taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Fexofenadine Hydrochloride RS in the Standard solution (mg/mL)

C_U = concentration of Fexofenadine Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous basis

4 OTHER COMPONENTS

Content of Chloride

Sample: 300 mg of Fexofenadine Hydrochloride

Blank: Methanol

Titrimetric system

(See Titrimetry 〈541〉.)

Mode: Direct titration

Titrant: 0.1 N silver nitrate VS

Endpoint detection: Potentiometrically

Analysis: Dissolve the Sample in 50 mL of methanol. Each mL of 0.1 N silver nitrate VS is equivalent to 3.545 mg of chloride.

Acceptance criteria: 6.45%–6.75% on the anhydrous basis

5 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Limit of Fexofenadine Related Compound B

Buffer: Glacial acetic acid and water (2.3: 2000). Adjust with 6 N ammonium hydroxide to a pH of 4.0 ± 0.1.

Mobile phase: Acetonitrile and Buffer (20:80)

System suitability solution: Add 1.2 mg of USP Fexofenadine Related Compound B RS to a 5-mL volumetric flask. Dilute with Mobile phase to volume. Transfer 2.0 mL of the solution into a 100-mL volumetric flask. Add 25 mg of USP Fexofenadine Hydrochloride RS, and dilute with Mobile phase to volume.

Standard solution: 2.5 μg/mL of USP Fexofenadine Hydrochloride RS in Mobile phase from the System suitability solution

Sample solution: 0.25 mg/mL of Fexofenadine Hydrochloride in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 25-cm; packing L45

Flow rate: 0.5 mL/min

Injection volume: 20 μL

System suitability

Sample: System suitability solution

[Note-The relative retention times for fexofenadine related compound B and fexofenadine are about 0.7 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 3.0 between fexofenadine and fexofenadine related compound B

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of fexofenadine related compound B in the portion of Fexofenadine Hydrochloride taken:

Result = (r_U /r_S ) × (C_S /C_U ) × (1/F) × 100

r_U = peak response for fexofenadine related compound B from the Sample solution

r_S = peak response for fexofenadine from the Standard solution

C_S = concentration of USP Fexofenadine Hydrochloride RS in the Standard solution (mg/mL)

C_U = concentration of fexofenadine in the Sample solution (mg/mL)

F = relative response factor for fexofenadine related compound B relative to fexofenadine, 0.8

Acceptance criteria: NMT 0.2%

Other Organic Impurities

Buffer, Diluent, Mobile phase, Standard solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Sample solution: Use the Sample stock solution in the Assay.

Reference solution: Use the Sample solution in the Assay.

Samples: Standard solution, Sample solution, Reference solution, and Mobile phase (used as the blank)

Measure the peak areas, excluding the peaks corresponding to those from the Mobile phase.

Calculate the percentage of fexofenadine related compound A in the portion of Fexofenadine Hydrochloride taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak response for fexofenadine related compound A from the Sample solution

r_S = peak response for fexofenadine related compound A from the Standard solution

C_S = concentration of USP Fexofenadine Related Compound A RS in the Standard solution (mg/mL)

C_U = concentration of fexofenadine in the Sample solution (mg/mL)

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:

Result = (r_U /r_S ) × (C_S /C_U ) × (1/F) × 100

r_U = peak response of the decarboxylated degradant from the Sample solution

r_S = peak response of fexofenadine from the Standard solution

C_S = concentration of USP Fexofenadine Hydrochloride RS in the Standard solution (mg/mL)

C_U = concentration of fexofenadine in the Sample solution (mg/mL)

F = relative response factor for the decarboxylated degradant relative to fexofenadine, 1.1

Calculate the percentage of other impurities in the portion of Fexofenadine Hydrochloride taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak response for any other impurity from the Sample solution

r_S = peak response of fexofenadine from the Reference solution

C_S = concentration of fexofenadine in the Reference solution (mg/mL)

C_U = concentration of fexofenadine in the Sample solution (mg/mL)

Acceptance criteria: See Table 1.

Table 1

^a Benzeneacetic acid, 4-[1-oxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-α,α-dimethyl.

^b (±)-4-[1-Hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl]-isopropylbenzene.

6 SPECIFIC TESTS

Water Determination, Method Ic 〈921〉: NMT 2.0% for the anhydrous form; 6.0%–10.0% for the hydrate form. [Note—“Hydrate” refers to a mixture of dihydrate and trihydrate forms of fexofenadine hydrochloride.]

7 ADDITIONAL REQUIREMENTS

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.

Change to read:

USP Reference Standards 〈11〉

USP Fexofenadine Hydrochloride RS

USP Fexofenadine Related Compound A RS

2-(4-{4-[4-(Hydroxydiphenylmethyl)piperidin-1-yl]butanoyl}phenyl)-2-methylpropanoic acid;

Also known as Benzeneacetic acid, 4-[1-oxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-α,α-dimethyl.

C₃₂H₃₇NO₄ 499.65

USP Fexofenadine Related Compound B RS

3-[1-Hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-α,α-dimethyl benzeneacetic acid hydrochloride monohydrate;

Also known as 2-(3-{1-Hydroxy-4-[4-(hydroxydiphenylmethyl)piperidin-1-yl]butyl}phenyl)-2-methylpropanoic acid hydrochloride monohydrate. (ERR 1-Feb-2021)

C₃₂H₃₉NO₄· HCl · H₂O 556.14 (ERR 1-Feb-2021)