Dolasetron Mesylate

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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C₁₉H₂₀N₂O₃ · CH₄O₂S · H₂O        438.49

1H-Indole-3-carboxylic acid, octahydro-3-oxo-2,6-methano-2H -quinolizin-8-yl ester, (2α,6α,8α,9aβ)-, monomethanesulfonate monohydrate;

Indole-3-carboxylic acid, ester with (8r)-hexahydro-8-hydroxy-2,6-methano-2H-quinolizin-3(4H)-one, monomethanesulfonate monohydrate CAS RN: 878143-33-0; UNII: U3C8E5BWKR.

Anhydrous CAS RN: 115956-13-3; UNII: 71YF100S3H.

1 DEFINITION

Dolasetron Mesylate contains NLT 98.0% and NMT 102.0% of C₁₉H₂₀N₂O₃ · CH₄O₂S · H₂O, calculated on the as-is basis.

2 IDENTIFICATION

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

B. PROCEDURE

Sample solution: 1 mg/mL

Analysis: Transfer 5-10 mg of 5,5'-methylenedisalicylic acid to a clean crucible, and heat in an oven at 150° for 5 min. Remove from the oven, and add 10 drops of the Sample solution. Return to the oven, and evaporate to dryness.

Acceptance criteria: A red or pink color (presence of methanesulfonic acid) develops in the white residue.

3 ASSAY

Change to read:

PROCEDURE

Solution A: Add 0.19 mL. of triethylamine to each 450 mL of acetonitrile. (ERR 1-Jun-2020)

Mobile phase: Solution A. (ERR 1-Jun-2020) water, and 1 M ammonium formate (450:440:110) _{(ERR 1-Jun-2020)}

Standard solution: 0.04 mg/mL and 0.004 mg/mL respectively of USP Dolasetron Mesylate RS and indole-3-carboxylic acid in Mobile phase

Sample solution: 0.04 mg/mL of Dolasetron Mesylate in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 285 nm

Column: 4.6-mm x 15-cm; packing L1

Flow rate: 1 mL/min

Injection size: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 4 between indole-3-carboxylic acid and dolasetron mesylate

Tailing factor: NMT 1.8

Relative standard deviation: NMT 1.5% for replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₁₉H₂₀N₂O₃ · CH₄O₂S · H₂O in the Dolasetron Mesylate 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 Dolasetron Mesylate RS in the Standard solution (mg/mL)

C_u = concentration of Dolasetron Mesylate in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the as-is basis

4 IMPURITIES

Organic Impurities

Procedure

0.01 M Dibasic ammonium phosphate solution: 1.32 g/L of dibasic ammonium phosphate. Adjust with 2.0 M phosphoric acid to a pH of7.0.

Diluent: Acetonitrile and water (1:4)

Solution A: Acetonitrile and 0.01 M Dibasic ammonium phosphate solution (53:1000), ltered and degassed

Solution B: Acetonitrile and 0.01 M Dibasic ammonium phosphate solution (795:295), ltered and degassed

Mobile phase: See the gradient table below.

System suitability solution: 0.004 mg/mL and 0.03 mg/ml, respectively, of indole and USP Dolasetron Mesylate RS in Diluent

Standard solution A: 0.03 mg/mL of USP Dolasetron Mesylate RS in Diluent

Polasetron Standard solution B: 6 mg/mL and 0.0072 mg/mL, respectively, of USP Dolasetron Mesylate RS and USP Dolasetron Mesylate Related

Compound A RS in Diluent

Sample solution: 6 mg/mL of Dolasetron Mesylate in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm x 25-cm; packing L7

Flow rate: 1.5 mL/min

Injection size: 100 µL

System suitability

Suitability requirements

Resolution: NLT 1.5 between the first eluting peak, indole, and the second eluting peak, dolasetron mesylate from the System suitability solution. [NOTE-If the dolasetron mesylate peak is found to elute before the indole peak, condition the column as follows: fill up the column with Solution A, plug the column, and place the column in a convection oven at 105° for about 16 h. Retest the column.]

Relative standard deviation: NMT 5.0% for replicate injections of Standard solution A

Analysis

Samples: Standard solution A, Standard solutionB, and Sample solution

Calculate the percentage of dolasetron mesylate related compound A in the Dolasetron Mesylate taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (M_r1 /M_r2 ) × 100

r_u = peak response of dolasetron mesylate related compound A from the Sample solution

r_s = peak response of dolasetron mesylate related compound A from the Standard solution B

C_s = concentration of USP Dolasetron Mesylate Related Compound A RS in the Standard solution B (mg/mL)

C_u = concentration of Dolasetron Mesylate in the Sample solution (mg/mL)

M_r1 = molecular weight of dolasetron mesylate related compound A base, 181.2

M_r2 = molecular weight of dolasetron mesylate related compound A hydrochloride, 217.8

Calculate the percentage of each impurity (other than dolasetron mesylate related compound A) in the portion of Dolasetron Mesylate taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of each impurity from the Sample solution

r_s = peak response of dolasetron mesylate from the Standard solution A

C_s = concentration of USP Dolasetron Mesylate RS in the Standard solution A (mg/mL)

C_u = concentration of Dolasetron Mesylate in the Sample solution (mg/mL)

Acceptance criteria

Individual impurities: NMT 0.1%

Total impurities: NMT 0.3%

[Note—The reporting level for impurities is 0.05%.]

5 SPECIFIC TESTS

WATER DETERMINATION, Method la(921): Between 3.5% and 4.7%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers, protected from light.

USP REFERENCE STANDARDS (11)

USP Dolasetron Mesylate RS

USP Dolasetron Mesylate Related Compound A RS

Hexahydro-8-hydroxy-2,6-methano-2H-quinolizin-3 (4H)-one, hydrochloride.