Hexylene Glycol

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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C₆H₁₄O₂      118.18 _{(NF 1-May-2020)}

2,4-Pentanediol, 2-methyl-;

2-Methyl-2,4-pentanediol;

2-Methylpentane-2,4-diol _{(NF 1-May-2020)} CAS RN: 107-41-5.

1 DEFINITION

Change to read:

Hexylene Glycol contains NLT 98.0% and NMT 102.0% of 2-methylpentane-2,4-diol, calculated on the anhydrous basis. _{(NF 1-May-2020)}

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197F _{(CN 1-May-2020)}

Sample: Undried specimen

Acceptance criteria: Meets the requirements

Add the following:

B. Chromatographic Identity

Analysis: Examine the chromatograms from the Assay.

Acceptance criteria: The retention time of the major peak of the Sample solution corresponds to that of the Standard solution. _{(NF 1-May-2020)}

3 ASSAY

Add the following:

Procedure

Diluent: Methanol

Internal standard solution: 1.0 mg/mL of USP Propylene Glycol RS (internal standard) in Diluent

System suitability solution: 0.1 mg/mL of diacetone alcohol and 1.0 mg/mL of USP Hexylene Glycol RS in Internal standard solution

Standard solution: 1.0 mg/mL of USP Hexylene Glycol RS in Internal standard solution

Sample solution: 1.0 mg/mL of Hexylene Glycol in Internal standard solution

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 0.32-mm × 60-m capillary; bonded with a 1.0-µm layer of phase G1

Temperatures

Injection port: 200°

Detector: 300°

Column: See Table 1.

Table 1

Carrier gas: Helium

Pressure: 15 psi (constant pressure mode)

Injection volume: 1.0 µL

Injection type: Split ratio, 100:1

Liner: Ultra inert liner with glass wool, low pressure drop¹

System suitability

Samples: System suitability solution and Standard solution

[Note—The approximate relative retention times are listed in Table 2.]

Suitability requirements

Resolution: NLT 5 between hexylene glycol and diacetone alcohol, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 2.0% for the peak response ratio of hexylene glycol to the internal standard, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of hexylene glycol in the portion of the sample taken:

Result = (R_u /R_s ) × (C_s /C_u ) × 100

R_u = peak response ratio of hexylene glycol to the internal standard (peak response of hexylene glycol/peak response of the internal standard) from the Sample solution

R_s = peak response ratio of hexylene glycol to the internal standard (peak response of hexylene glycol/peak response of the internal standard) from the Standard solution

C_s = concentration of USP Hexylene Glycol RS in the Standard solution (mg/mL)

C_u = concentration of Hexylene Glycol in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous basis _{(NF 1-May-2020)}

4 IMPURITIES

Change to read:

Organic Impurities

Diluent and Chromatographic system: Proceed as directed in the Assay.

Sensitivity solution: 0.01 mg/mL of USP Hexylene Glycol RS in Diluent

System suitability solution: 0.2 mg/mL of USP Acetone RS and 0.2 mg/mL of USP 2-Propanol RS in Diluent

Standard solution: 0.02 mg/mL of USP Hexylene Glycol RS in Diluent

Sample solution: 20.0 mg/mL of Hexylene Glycol in Diluent

System suitability

Samples: Sensitivity solution, System suitability solution, and Standard solution

[Note—The approximate relative retention times are listed in Table 2.]

Suitability requirements

Resolution: NLT 1.5 between the acetone peak and the 2-propanol peak, System suitability solution

Relative standard deviation: NMT 5.0%, determined from the hexylene glycol peak, Standard solution

Signal-to-noise ratio: NLT 10, determined from the hexylene glycol peak, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual impurity in the portion of the sample taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (1/F) × 100

r_u = peak area of each individual impurity from the Sample solution

r_s = peak area of hexylene glycol from the Standard solution

C_s = concentration of USP Hexylene Glycol RS in the Standard solution (mg/mL)

C_u = concentration of Hexylene Glycol in the Sample solution (mg/mL)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2.

Table 2

^a 4-Hydroxy-4-methylpentan-2-one.

5 SPECIFIC TESTS

SPECIFIC GRAVITY (841): 0.917-0.923

REFRACTIVE INDEX (831): 1.424-1,430

ACIDITY

Sample: 10 mL

Analysis: Mix 1 mL of phenolphthalein TS with 50 mL of water, and add 0.1 N sodium hydroxide until the solution remains pink for 30 s. Add the Sample, and titrate with 0.10 N sodium hydroxide until the original pink color returns and remains for 30 s.

Acceptance criteria: NMT 0.20 mL of 0.10 N sodium hydroxide is required.

WATER DETERMINATION (921), Method: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

Change to read:

USP REFERENCE STANDARDS (11)

USP Acetone B (NF 1-May-2020)

USP Hexylene Glycol RS

USP 2-Propanol RS

USP Propylene Glycol _{(NF 1-May-2020)}

¹ Agilent PN 5190-3165 liner has been suitable. Other equivalent liners are also suitable.