Triethyl Citrate

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

Triethyl Citrate contains NLT 97.0% and NMT 102.0% (NF 1-May-2023) of triethyl citrate (C₁₂H₂₀O₇), calculated on the anhydrous basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS 〈197〉 , Infrared Spectroscopy: 197F Change to read:

B. CHROMATOGRAPHIC IDENTITY: (NF 1-M  -2023) The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, (NF 1-May-2023) as obtained in the Assay.

3 ASSAY

Change to read:

PROCEDURE

Diluent: Methylene chloride

Internal standard solution: 1 mg/mL of trimethyl citrate in Diluent

Standard solution: 1 mg/mL of USP Triethyl Citrate RS in Internal standard solution Sample solution: 1 mg/mL of Triethyl Citrate in Internal standard solution

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 0.32-mm × 30-m; 0.5-µm layer of phase G42

Temperatures

Injector: 225°

Detector: 275° Column: See Table 1.

Table 1

Carrier gas: Helium Flow rate: 2.3 mL/min

Injection volume: 1 µL

Injection type: Split, split ratio 30:1

System suitability

Sample: Standard solution

[NOTE—The retention time for triethyl citrate is about 14.6 min. The relative retention times for trimethyl citrate and triethyl citrate are 0.9 and 1.0, respectively.]

Suitability requirements

Tailing factor: NMT 1.5 for the triethyl citrate and (ERR 1-May-2023) trimethyl citrate peaks Relative standard deviation: NMT 1.0% of the peak area ratio of triethyl citrate to trimethyl citrate

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of triethyl citrate (C₁₂H₂₀O₇) in the portion of Triethyl Citrate taken:

Result = (R_U/R_S) × (C_S/C_U) × 100

R_U = peak area ratio of triethyl citrate to trimethyl citrate from the Sample solution

R_S = peak area ratio of triethyl citrate to trimethyl citrate from the Standard solution

C_S = concentration of USP Triethyl Citrate RS in the Standard solution (mg/mL)

C_U = concentration of Triethyl Citrate in the Sample solution (mg/mL)

Acceptance criteria: 97.0%–102.0% on the anhydrous basis (NF 1-May-2023)

Add the following:

4 IMPURITIES

ORGANIC IMPURITIES

Diluent and Chromatographic system: Proceed as directed in the Assay. Standard solution A: 0.02 mg/mL of USP Triethyl Aconitate RS in Diluent Standard solution B: 0.02 mg/mL of USP Triethyl Citrate RS in Diluent Sample solution: 10 mg/mL of Triethyl Citrate in Diluent

System suitability

Samples: Standard solution A and Standard solution B Suitability requirements

Relative standard deviation: NMT 3.0% for the triethyl aconitate peak, Standard solution A; NMT 3.0% for the triethyl citrate peak, Standard solution B

Analysis

Samples: Standard solution A, Standard solution B, and Sample solution [NOTE—See Table 2 for the relative retention times.]

Table 2

^a Triethyl (E)-prop-1-ene-1,2,3-tricarboxylate.

Calculate the percentage of triethyl aconitate in the portion of Triethyl Citrate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak area of triethyl aconitate from the Sample solution

r_S = peak area of triethyl aconitate from Standard solution A

C_S = concentration of USP Triethyl Aconitate RS in Standard solution A (mg/mL)

C_U = concentration of Triethyl Citrate in the Sample solution (mg/mL)

Calculate the percentage of each individual impurity, excluding any solvent peaks, in the portion of Triethyl Citrate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

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

r_S = peak area of triethyl citrate from Standard solution B

C_S = concentration of USP Triethyl Citrate RS in Standard solution B (mg/mL)

C_U = concentration of Triethyl Citrate in the Sample solution (mg/mL)

Acceptance criteria

Triethyl aconitate: NMT 0.2% Individual impurity: NMT 0.2%

Total impurities: NMT 0.5% (NF 1-May-2023)

5 SPECIFIC TESTS

Delete the following:

SPECIFIC GRAVITY 〈841〉 (NF 1-May-2023)

Delete the following:

REFRACTIVE INDEX 〈831〉 (NF 1-May-2023)

ACIDITY

Neutralized isopropyl alcohol: To a suitable quantity of isopropyl alcohol add 2–3 drops of bromothymol blue TS and just sufficient 0.10 N sodium hydroxide dropwise to produce a faint blue color. [NOTE—Prepare Neutralized isopropyl alcohol just prior to use.]

Sample solution: 32.0 g of Triethyl Citrate in 30 mL of Neutralized isopropyl alcohol

Analysis: Add bromothymol blue TS, and titrate with 0.10 N sodium hydroxide to a faint blue endpoint. Acceptance criteria: NMT 1.0 mL of 0.10 N sodium hydroxide is required.

WATER DETERMINATION 〈921〉 , Method I: NMT 0.25%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

Change to read:

USP REFERENCE STANDARDS 〈11〉

USP Triethyl Aconitate RS (NF 1-May-2023)

USP Triethyl Citrate RS