Doxapram 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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C₂₄H₃₀N₂O₂ · HCl · H₂O 432.99

C₂₄H₃₀N₂O₂ · HCl 414.97

2-Pyrrolidinone, 1-ethyl-4-[2-(4-morpholinyl)ethyl]-3,3-diphenyl-, monohydrochloride, monohydrate, (±)-;

(+)-1-Ethyl-4-(2-morpholinoethyl)-3,3-diphenyl-2-pyrrolidinone monohydrochloride monohydrate CAS RN: 7081-53-0: UNII: P5RU6U0Q5Y.

Anhydrous CAS RN: 113-07-5; UNII: FB8713U6DM.

1 DEFINITION

Doxapram Hydrochloride, dried at 105° for 2 h, contains NLT 98.0% and NMT 102.0% of doxapram hydrochloride (C₂₄H₃₀N₂O₂ · HCl).

2 IDENTIFICATION

Change to read:

A.SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K _{(CN 1-MAY-2020)}

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

C. IDENTIFICATION TESTS GENERAL (191), Chloride: Meets the requirements

3 ASSAY

PROCEDURE

Solution A: To each L. of water, add 0.1 mL of trifluoroacetic acid..

Solution B: To each L of acetonitrile, add 0.1 mL of trifluoroacetic acid.

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (30:70)

Standard solution: 0.2 mg/mL of USP Doxapram Hydrochloride RS in Diluent

Sample solution: 0.2 mg/mL of Doxapram Hydrochloride in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 5-cm; 2.5-µm packing L1

Column temperature: 35°

Flow rate: 1.0 mL/min

Injection volume: 5 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of doxapram hydrochloride (C₂₄H₃₀N₂O₂ · HCl) in the portion of Doxapram Hydrochloride taken:

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

r_u = peak response of doxapram from the Sample solution

r_s = peak response of doxapram from the Standard solution

C_s = concentration of USP Doxapram Hydrochloride RS in the Standard solution (mg/mL)

C_u = concentration of Doxapram Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0%, previously dried at 105° for 2 h

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.3%

ORGANIC IMPURITIES

Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: 2 mg/mL of USP Doxapram Hydrochloride RS and 0.04 mg/mL of USP Doxapram Related Compound B RS in Diluent

Standard solution: 0.004 mg/mL each of USP Doxapram Hydrochloride RS and USP Doxapram Related Compound B RS in Diluent

Sample solution: 2 mg/mL of Doxapram Hydrochloride in Diluent

System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 2 for relative retention times.]

Suitability requirements

Resolution: NLT 1.5 between doxapram related compound B and doxapram, System suitability solution

Relative standard deviation: NMT 5.0% for doxapram related compound B and doxapram, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of doxapram related compound B in the portion of Doxapram Hydrochloride taken:

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

r_u = peak response of doxapram related compound B from the Sample solution

r_s = peak response of doxapram related compound B from the Standard solution

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

C_u = concentration of Doxapram Hydrochloride in the Sample solution (mg/mL)

Calculate the percentage of doxapram chloroethyl analog or any individual unspecied impurity in the portion of Doxapram Hydrochloride taken:

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

r_u = peak response of doxapram chloroethyl analog or any individual unspecied impurity from the Sample solution

r_s = peak response of doxapram from the Standard solution

C_s = concentration of USP Doxapram Hydrochloride RS in the Standard solution (mg/mL)

C_u = concentration of Doxapram Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. Disregard any peak below 0.05%.

Table 2

^a 4-(2-Chloroethyl)-1-ethyl-3,3-diphenylpyrrolidin-2-one.

5 SPECIFIC TESTS

pH 〈791〉

Sample solution: 10 mg/mL of Doxapram Hydrochloride in water

Acceptance criteria: 3.5–5.0

Loss on Drying 〈731〉

Analysis: Dry at 105° for 2 h.

Acceptance criteria: 3.0%–4.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Doxapram Hydrochloride RS

USP Doxapram Related Compound B RS

1-Ethyl-4-{2-[(2-hydroxyethyl)amino]ethyl}-3,3-diphenylpyrrolidin-2-one hydrochloride.

C₂₂H₂₉CIN₂O₂             388.93