Articaine Hydrochloride

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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C₁₃H₂₀N₂O₃S.HCI  320.83

2-Thiophenecarboxylic acid, 4-methyl-3-{[1-oxo-2-(propylamino)propyl]amino)-, methyl ester, monohydrochloride; (CN 1-Aug-2024)

Methyl 4-methyl-3-[2-(propylamino)propionamido]-2-thiophenecarboxylate, monohydrochloride CAS RN^®: 23964-57-0; UNII: QS9014Q792.

1 DEFINITION

Articaine Hydrochloride contains NLT 98.5% and NMT 101.0% of C13H20N2O3S HCI, calculated on the dried basis.

2 IDENTIFICATION

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

Standard solution: 12 mg/mL of USP Articaine RS in methylene chloride. Transfer 20 µL of this solution onto a 300-mg disk.

Sample solution: Dissolve 100 mg of Articaine Hydrochloride in 5 mL of water. Add 3 mL of a saturated solution of sodium bicarbonate, and shake twice with 2 mL of methylene chloride. Combine the methylene chloride layers, dilute with methylene chloride to 5.0 mL, and dry over anhydrous sodium sulphate. Transfer 20 µL of this solution onto a 300-mg disk.

2.2 B. IDENTIFICATION TESTS-GENERAL, Chloride (191)

3 ASSAY

3.1 PROCEDURE

Sample solution: 250 mg of Articaine Hydrochloride to a 250-mL conical flask. Add 5.0 mL of 0.01 M hydrochloric acid and 50 mL of alcohol. Stir to dissolve.

Analysis: Titrate with 0.1 M sodium hydroxide VS, determining the endpoint potentiometrically, using a glass electrode. Calculate the volume of sodium hydroxide consumed by reading the volume added between the two points of inflection. Each mL of 0.1 M sodium hydroxide is equivalent to 32.08 mg of C₁₃H₂₀N₂O₃S.HCI.

Acceptance criteria: 98.5%-101.0% on the dried basis.

4 IMPURITIES

4.1 INORGANIC IMPURITIES

RESIDUE ON IGNITION (281)

Sample: 1 g

Acceptance criteria: NMT 0.1%

4.2 ORGANIC IMPURITIES

PROCEDURE

Buffer solution: 2.02 g of sodium 1-heptanesulfonate and 4.08 g of potassium dihydrogen phosphate in 1 L of water. Adjust with phosphoric acid to a pH of 2.0.

Mobile phase: Acetonitrile and Buffer solution (1:3)

Standard solution: 2 µg/mL of USP Articaine Related Compound A, and 1 µg/mL each of USP Articaine Related Compound E RS and USP Articaine Hydrochloride RS in Mobile phase. [NOTE-This solution is also used to determine the reporting threshold limit.]

Sample solution: 1.0 mg/mL of Articaine Hydrochloride in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 276 nm

Column: 4.6-mm x 25-cm; packing L1

Temperature: 45°

Flow rate: 1 mL/min

Injection size: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 1.2 between articaine related compound A and articaine related compound E

Analysis

Samples: Standard solution and Sample solution. [NOTE-Run time is 5 times the retention time of articaine.]

Calculate the percentage of any articaine related compound A in the portion of Articaine Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = response of articaine related compound A from the Sample solution

r_S = response of articaine related compound A from the Standard solution

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

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

Calculate the percentage of each individual impurity in the portion of Articaine Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = response of each individual impurity from the Sample solution

r_S = response of articaine hydrochloride from the Standard solution

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

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

[NOTE-Disregard any peak below 0.05%.]

Acceptance criteria

Individual impurities: See Impurity Table 1.

Total impurities: NMT 0.5%. [NOTE-Excluding articaine related compound A.]

Impurity Table 1

^a 4-Methyl-3-[[(2RS)-2-(propylamino)propanoyl)amino]thiophene-2-carboxylic acid.

^b Methyl 3-[[(2RS)-2-(ethylamino)propanoyl)amino]-4-methylthiophene-2-carboxylate.

^c Methyl 4-methyl-3-[2-(propylamino) acetamido]thiophene-2-carboxylate.

^d Methyl 3-[2-(isopropylamino)propanamido]-4-methylthiophene-2-carboxylate.

^e 4-Methyl-N-propyl-3-[[(2RS)-2-(propylamino) propanoyl)amino]thiophene-2-carboxamide.

^f Methyl 3-[[(2RS)-2-(butylamino)propanoyl]amino]-4-methylthiophene-2-carboxylate.

^g Methyl 3-[[(2RS)-2-(dipropylamino) propanoyl)amino]-4-methylthiophene-2-carboxylate.

^h Methyl 3-amino-4-methylthiophene-2-carboxylate.

ⁱ 1-Methylethyl 4-methyl-3-[[(2RS)-2-(propylamino)propanoyl]amino] thiophene-2-carboxylate.

^j Methyl 3-[[(2RS)-2-bromopropanoyl)amino]-4-methylthiophene-2-carboxylate.

5 SPECIFIC TESTS

LOSS ON DRYING (731): Dry at 105° for 5 h: it loses NMT 0.5% of its weight.

PH (791).

Sample solution: 10 mg/mL

Acceptance criteria: 4.2-5.2

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in light-resistant containers.

Change to read:

0.10

6.2 USP REFERENCE STANDARDS (11)

USP Articaine RS

USP Articaine Hydrochloride RS

USP Articaine Related Compound A RS

Methyl 4-methyl-3-[2-(propylamino) acetamido]thiophene-2-carboxylate hydrochloride.

C₁₂H₁₈N₂O₃S HCI  306.81 (CN 1-Aug-2024)

USP Articaine Related Compound E RS

Methyl 3-[2-(isopropylamino) propanamido]-4-methylthiophene-2-carboxylate.

C₁₃H₂₀N₂O₃S  284.37