Doxapram Hydrochloride Injection

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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1 DEFINITION

Doxapram Hydrochloride Injection is a sterile solution of Doxapram Hydrochloride in Water for Injection. It contains NLT 90.0% and NMT 110.0% of the labeled amount of doxapram hydrochloride monohydrate  (C₂₄H₃₀N₂O₂ · HCl · H₂O).

2 IDENTIFICATION

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

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

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: Nominally 0.2 mg/mL of doxapram hydrochloride monohydrate, equivalent to 0.19 mg/mL of doxapram hydrochloride from Injection in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm. For Identication test B, use a diode array detector in the range of 190–300 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 1.0%

Analysis

amples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of doxapram hydrochloride monohydrate (C₂₄H₃₀N₂O₂ · HCl · H₂O) in the portion of Injection taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (M_r1 /M_r2 ) × 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 = nominal concentration of doxapram hydrochloride monohydrate in the Sample solution (mg/mL)

M_r1 = molecular weight of doxapram hydrochloride monohydrate, 432.99

M_r2 = molecular weight of anhydrous doxapram hydrochloride, 414.97

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

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 of USP Doxapram Hydrochloride RS in Diluent

Sample solution: Nominally 2 mg/mL of doxapram hydrochloride monohydrate, equivalent to 1.9 mg/mL of doxapram hydrochloride from Injection 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%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of doxapram related compound B, doxapram chloroethyl analog, or any individual unspecified degradation product in the portion of Injection taken:

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

r_u = peak response of each corresponding 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 = nominal concentration of doxapram hydrochloride monohydrate in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. Disregard any peak below 0.1%.

Table 2

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

5 SPECIFIC TESTS

pH 〈791〉: 3.5–5.0

Bacterial Endotoxins Test 〈85〉: It contains NMT 3.3 USP Endotoxin Units/mg of doxapram hydrochloride.

Other Requirements: It meets the requirements in Injections and Implanted Drug Products 〈1〉.

ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose or multiple-dose containers, preferably of Type I glass. Store at controlled room temperature.

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