Acetyltriethyl Citrate

C₁₄H₂₂O₈  318.32

Citric acid, O-acetyltriethyl ester;

Triethyl 2-acetoxypropane-1,2,3-tricarboxylate; CAS RN®: 77-89-4.

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1 DEFINITION

Acetyltriethyl Citrate contains NLT 98.0% and NMT 102.0% (NF 1-May-2023) of acetyltriethyl citrate ( C₁₄H₂₂O₈), calculated on the anhydrous basis.

2 IDENTIFICATION

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

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B. CHROMATOGRAPHIC IDENTITY (NF 1-May-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

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4 PROCEDURE

Diluent: Methylene chloride

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

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

Sample solution: 1 mg/mL of Acetyltriethyl 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.

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 acetyltriethyl citrate is about 15.4 min. The relative retention times for trimethyl citrate and acetyltriethyl citrate are 0.88 and 1.0, respectively.]

Suitability requirements

 Tailing factor: NMT 1.5 for the acetyltriethyl citrate and trimethyl citrate peaks

 Relative standard deviation: NMT 1.0% of the peak area ratio of acetyltriethyl citrate to trimethyl citrate

Analysis

 Samples: Standard solution and Sample solution

Calculate the percentage of acetyltriethyl citrate (C₁₄H₂₂O₈) in the portion of Acetyltriethyl Citrate taken:

Result = (RU/RC) × (CS/CC) × 100

RU = peak area ratio of acetyltriethyl citrate to trimethyl citrate from the Sample solution

 RS = peak area ratio of acetyltriethyl citrate to trimethyl citrate from the Standard solution

 CS = concentration of USP Acetyltriethyl Citrate RS in the Standard solution (mg/mL)

 CC = concentration of Acetyltriethyl Citrate in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous basis (NF 1-May-2023)

Add the following:

5 IMPURITIES

ORGANIC IMPURITIES

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

 Standard solution A: 0.05 mg/mL of USP Triethyl Aconitate RS in Diluent

 Standard solution B: 0.03 mg/mL of USP Triethyl Citrate RS in Diluent

 Standard solution C: 0.03 mg/mL of USP Acetyltriethyl Citrate RS in Diluent

 Sample solution: 10 mg/mL of Acetyltriethyl Citrate in Diluent

System suitability

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

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)

  NMT 3.0% for the acetyltriethyl citrate peak (Standard solution C)

Analysis

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

[NOTE—See Table 2 for the relative retention times.]

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

Calculate the percentage of triethyl aconitate or triethyl citrate:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak area from the Sample solution

 r_S = peak area from Standard solution A or B

 C_S = concentration in Standard solution A or B (mg/mL)

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

Calculate the percentage of each individual impurity:

Result = (r_U/r_C) × (C_S/C_U) × 100

r_U = peak area of impurity

 r_C = peak area of acetyltriethyl citrate from Standard solution C

 C_S = concentration of USP Acetyltriethyl Citrate RS in Standard solution C (mg/mL)

 C_U= concentration in Sample solution (mg/mL)

Acceptance criteria

 Triethyl aconitate: NMT 0.5%

 Triethyl citrate: NMT 0.3%

 Individual impurity: NMT 0.3%

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

6 SPECIFIC TESTS

Delete the following:

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

Delete the following:

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

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  ACIDITY

Neutralized isopropyl alcohol: To a suitable quantity of isopropyl alcohol add 2–3 drops of bromothymol blue TS and 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 (NF 1-May-2023)

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 0.3%

7 ADDITIONAL REQUIREMENTS

  PACKAGING AND STORAGE: Preserve in tight containers.

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  USP REFERENCE STANDARDS 〈11〉

 USP Acetyltriethyl Citrate RS

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

 USP Triethyl Citrate RS