Acarbose

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

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

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C₂₅H₄₃NO₁₈ 645.60

D-Glucose, 0-4,6-dideoxy-4-[[[1S-(1α, 4α,5β,6α)]-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexen-1-yl)amino]-α-D-glucopyranosyl-(1→4)-O-α-D-glucopyranosyl-(1→4)-;

O-4,6-Dideoxy-4-{[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexen-1-yl)amino)-α-D-glucopyranosyl-(1→4)-0-α-D-glucopyranosyl-(1→4)-D-glucose CAS RN^®: 56180-94-0; UNII: T58MSI464G.

1 DEFINITION

Acarbose is produced by certain strains of Actinoplanes utahensis. It contains NLT 95.0% and NMT 102.0% of acarbose (C₂₅H₄₃NO₁₈), calculated on the anhydrous basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K

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

3 ASSAY

3.1 PROCEDURE

Solution A: 0.6 mg/mL of monobasic potassium phosphate and 0.35 mg/mL of dibasic sodium phosphate in water

Mobile phase: Acetonitrile and Solution A (3:1)

System suitability solution: 20 mg/mL of USP Acarbose System Suitability Mixture RS in water

Standard solution: 20 mg/mL of USP Acarbose RS in water

Sample solution: 20 mg/mL of Acarbose in water

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4-mm x 25-cm; packing L8

Column temperature: 35°

Flow rate: 2 mL/min

Injection volume: 10 µL

3.2 System suitability

Sample: System suitability solution

Identify the acarbose peak and the peaks due to the impurities listed in Table 1.

Suitability requirements

Peak-to-valley ratio: The ratio of the height of the impurity A peak to the height of the valley between the impurity A peak and the acarbose peak is NLT 1.2.

Chromatogram comparability: The chromatogram obtained is similar to the chromatogram provided with USP Acarbose System Suitability Mixture RS for the known impurities found.

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of acarbose (C₂₅H₄₃NO₁₈) in the portion of Acarbose 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 Acarbose RS in the Standard solution (mg/mL)

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

Acceptance criteria: 95.0%-102.0% on the anhydrous basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

Sample: 1.0 g

Acceptance criteria: NMT 0.2%

4.2 Change to read:

CHROMATOGRAPHIC PURITY

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

Diluted sample solution: Dilute 1.0 mL of the Sample solution with water to 100.0 mL.

Analysis

Samples: Sample solution and Diluted sample solution

Calculate the percentage of each impurity in the portion of Acarbose taken:

Result = (r_U/r_A) × (1/F)

r_U = peak response of each impurity from the Sample solution

r_A = peak response of the main acarbose peak from the Diluted sample solution

F = relative response factor for each impurity (see Table 1)

Acceptance criteria: See Table 1.

^a O-4,6-Dideoxy-4-{[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl) cyclohex-2-enyl)amino)-α-D-glucopyranosyl-(1→4)-O-α-D-glucopyranosyl-(1→4)-D-arabino-hex-2-ulopyranose.

^b (1R,4R,5S,6R)-4,5,6-Trihydroxy-2-(hydroxymethyl) cyclohex-2-enyl 4-O-[4,6-dideoxy-4-{[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl) cyclohex-2-enyl)amino)-α-D-glucopyranosyl]-α-D-glucopyranoside.

^c a-D-Glucopyranosyl 4-O-[4,6-dideoxy-4-{[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl) cyclohex-2-enyl)amino)-α-D-glucopyranosyl]-α-D-glucopyranoside.

^d 4-O-[4,6-Dideoxy-4-{[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl) cyclohex-2-enyl]amino)-α-D-glucopyranosyl]-D-glucopyranose.

^e O-4,6-Dideoxy-4-{[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl) cyclohex-2-enyl]amino}-α-D-glucopyranosyl-(1→4)-O-α-D-glucopyranosyl-(1→4)-O-α-D-glucopyranosyl-(1→4)-D-arabino-hex-2-ulopyranose (4-O-α-acarbosyl-D-fructopyranose).

^f O-4,6-Dideoxy-4-{[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl) cyclohex-2-enyl]amino)-α-D-glucopyranosyl-(1→4)-O-α-D-glucopyranosyl-(1→4)-O-α-D-glucopyranosyl-(1→4)-D-glucopyranose (4-O-α-acarbosyl-D-glucopyranose).

^g α-D-Glucopyranosyl 0-4,6-dideoxy-4-{[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl) cyclohex-2-enyl]amino)-α-D-glucopyranosyl-(1→4)-O-α-D-glucopyranoside (α-D-glucopyranosyl α-acarboside).

^h O-4,6-Dideoxy-4-{[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-enyl]amino)-α-D-glucopyranosyl-(1→4)-O-6-deoxy-α-D-glucopyranosyl-(1→4)-D-glucopyranose.

5 SPECIFIC TESTS

5.1 OPTICAL ROTATION, Specific Rotation(781S)

Sample solution: 10 mg/mL in water

Acceptance criteria: +168° to +183°

5.2 PH (791)

Sample solution: 50 mg/mL

Acceptance criteria: 5.5-7.5

5.3 WATER DETERMINATION, Method Ic(921)

NMT 4.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

USP REFERENCE STANDARDS (11).

USP Acarbose RS

USP Acarbose System Suitability Mixture RS