Azeotropic Isopropyl Alcohol

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

Azeotropic Isopropyl Alcohol contains NLT 91.0% and NMT 93.0% of isopropyl alcohol, by volume, the remainder consisting of water.

2 IDENTIFICATION

2.1 A. INFRARED ABSORPTION

The IR absorption spectrum of a thin film of it exhibits a strong broad band at 3.0 µm; a strong region of absorption between 3.35 and 3.5 µm, with its highest peak at 3.36 µm, and others at 3.41 and 3.47 µm; many weak peaks between 3.6 and 6.0 µm, among the most noticeable being those at 3.68, 3.77, 3.97, 4.17, and 5.26 µm; a broad band at 6.2 µm; a strong region of absorption between 6.7 and 7.8 µm, the most prominent features being the peaks at 6.80, 7.09, 7.25 (the highest), 7.46, and 7.63 µm; a strong region of absorption between 8.5 and 9.2 µm, peaking at 8.6, 8.85, and 9.0 µm; and strong peaks at 10.5 and 12.3 µm.

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2.2 B. LIMIT OF METHANOL

[NOTE-This test must be performed to be in compliance with USP, in addition to Identification A above.]

System suitability solution, Sample solution, Standard solution A, Chromatographic system, and System suitability: Proceed as directed in the Volatile Impurities test.

Analysis: Proceed as directed in the Volatile Impurities test, Methanol calculation.

Acceptance criteria: Meets the requirements in Table 3 for methanol (RB 1-Feb-2022)

3 IMPURITIES

3.1 LIMIT OF NONVOLATILE RESIDUE

Sample: 50 mL

Analysis: Evaporate the Sample in a tared porcelain dish on a steam bath to dryness, and heat at 105° for 1 h.

Acceptance criteria: The weight of the residue does not exceed 2.5 mg (0.005%).

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3.2 VOLATILE IMPURITIES

System suitability solution: 200 µL/L of methanol and 1000 µL/L of ethyl acetate in (RB 1-Feb-2022) USP 2-Propanol System Suitability RS

Sample solution: Azeotropic Isopropyl Alcohol (Substance under test)

Standard solution A: 200 µL/L of methanol in Sample solution

[NOTE-To be performed as a part of Identification B.]

Standard solution B: 1000 µL/L each of acetone, diisopropyl ether, ethyl ether, 1-propanol, 2-butanol, and ethyl acetate in Sample solution

(RB 1-Feb-2022)

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: GC

Detector: Flame ionization (RB 1-Feb-2022)

Column: 0.25 - mm * 60 - m coated with a 1.4-µm film of phase G43

Temperature

Injector: 150°

Detector: 200°

Column: See Table 1.

Table 1

Carrier gas: Helium

Flow rate: 2.3mL / m * i n angle (RB 1-Feb-2022)

Injection volume: (RB 1-Feb-2022) 1mu*L

Injection type: Split injection; split ratio is about 50:1. [NOTE-A 4-mm straight liner is suitable.] (RB 1-FEB-2022)

Run time: 26 (RB 1-Feb-2022) min

System suitability

Sample: System suitability solution

[NOTE-See Table 2.]

Table 2

^a Ethyl acetate Reference Standard is not a known impurity. It is used for the calculation of unspecified impurities only.

Suitability requirements

Resolution: NLT 1.5 between acetone and isopropyl alcohol

Signal-to-noise ratio: NLT 10 for any of the following peaks: methanol, (RB 1-Feb-2022) ethyl ether, acetone, isopropyl alcohol, diisopropyl ether, 1-propanol, 2-butanol, and ethyl acetate. (RB 1-Feb-2022)

Tailing factor: NMT 2.0 for the isopropyl alcohol peak

Relative standard deviation: NMT 2.0% for the isopropyl alcohol peak of 6 replicate injections of System suitability solution (RB 1-Feb-2022)

Analysis

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

Methanol calculation

[NOTE-To be performed as a part of Identification B.]

Result (%v/v)= {[M_U/(M_S - M_U)] x C_M}/10,000

M_U = peak area of methanol in the Sample solution

M_S = peak area of methanol in Standard solution A

C_M = concentration of spiked methanol in Standard solution A (µL/L)

Individual known impurity (ethyl ether, acetone, diisopropyl ether, 1-propanol, 2-butanol) calculation

Result (% v/v) = {[K_U/(K_S - K_U)] x C_K}/10,000

K_U = peak area of individual known impurity in the Sample solution

K_S = peak area of individual known impurity in Standard solution B

C_K = concentration of spiked individual known impurity in Standard solution B (µL/L)

Individual unspecified impurity calculation

Result (%v/v)= [(r_U/r_S) x C_S]/10,000

r_U = peak area of each unspecified impurity in the Sample solution

r_S = peak area of ethyl acetate in Standard solution B

C_S = concentration of ethyl acetate in Standard solution B (µL/L) (RB 1-Feb-2022)

Acceptance criteria: See Table 3.

Table 3

^a To be performed as a part of Identification B.

4 SPECIFIC TESTS

SPECIFIC GRAVITY (841): 0.815-0.810, indicating 91.0%-93.0% of isopropyl alcohol (C₂H₂O) by volume

REFRACTIVE INDEX (831): 1.376-1.378 at 20°

ACIDITY

Sample: 50 mL

Analysis: Place the Sample in a suitable flask, and add 100 mL of carbon dioxide-free water. Add 2 drops of phenolphthalein TS, and titrate with 0.020 N sodium hydroxide to a pink color that persists for 30 s.

Acceptance criteria: NMT 0.70 mL of 0.020 N sodium hydroxide is required for neutralization.

5 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, remote from heat.

USP REFERENCE STANDARDS (11)

USP 2-Propanol System Suitability RS

It is a mixture of the following: ethyl ether (0.1%), acetone (0.1%), diisopropyl ether (0.1%), 1-propanol (0.1%), 2-butanol (0.1%), and isopropyl alcohol (99.5%).