Printed on: Thu Feb 09 2023, 01:02:09 AM(EST) Status: Not Yet Official on 09-Feb-2023 DocId: GUID-4CF097A8-66E5-4CE8-919D-669B5EEB1541_5_en-US

Printed by: Dang Van Vu Official Date: 01-May-2023 Document Type: NF @2023 USPC
Do Not Distribute DOI Ref: j8h8u DOI: https://doi.org/10.31003/USPNF_M675_05_01
1

Carrier gas: Helium

Acetyltriethyl Citrate 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

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Relative standard deviation: NMT 1.0% of the peak
area ratio of acetyltriethyl citrate to trimethyl citrate
Analysis
Samples: Standard solution and Sample solution
C14H22O8 318.32 Calculate the percentage of acetyltriethyl citrate (C14H22O8)

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Citric acid, O-acetyltriethyl ester; in the portion of Acetyltriethyl Citrate taken:
Triethyl 2-acetoxypropane-1,2,3-tricarboxylate; CAS RN®:
77-89-4. Result = (RU/RS) × (CS/CU) × 100

RU = peak area ratio of acetyltriethyl citrate to trimethyl

Change to read:

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citrate from the Sample solution
DEFINITION RS = peak area ratio of acetyltriethyl citrate to trimethyl
Acetyltriethyl Citrate contains ▲NLT 98.0% and NMT citrate from the Standard solution
102.0%▲ (NF 1-May-2023) of acetyltriethyl citrate (C14H22O8), CS = concentration of USP Acetyltriethyl Citrate RS in
the Standard solution (mg/mL)
calculated on the anhydrous basis.
CU = concentration of Acetyltriethyl Citrate in the
IDENTIFICATION
O Sample solution (mg/mL)
• A. SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared
Spectroscopy: 197F Acceptance criteria: 98.0%–102.0% on the anhydrous
basis▲ (NF 1-May-2023)
Change to read:
Add the following:
• B. ▲CHROMATOGRAPHIC IDENTITY:▲ (NF 1-May-2023) The
e
retention time of the major peak of the Sample solution ▲
IMPURITIES
corresponds to that of the ▲Standard solution,▲ (NF 1-May-2023) • ORGANIC IMPURITIES
as obtained in the Assay. Diluent and Chromatographic system: Proceed as
directed in the Assay.
B

ASSAY Standard solution A: 0.05 mg/mL of USP Triethyl Aconitate

Change to read: RS in Diluent
Standard solution B: 0.03 mg/mL of USP Triethyl Citrate
• PROCEDURE RS in Diluent
▲
Diluent: Methylene chloride Standard solution C: 0.03 mg/mL of USP Acetyltriethyl
Internal standard solution: 1 mg/mL of trimethyl citrate in Citrate RS in Diluent
To

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

Standard solution: 1 mg/mL of USP Acetyltriethyl Citrate Diluent
RS in Internal standard solution System suitability
Sample solution: 1 mg/mL of Acetyltriethyl Citrate in Samples: Standard solution A, Standard solution B, and
Internal standard solution Standard solution C
Chromatographic system Suitability requirements
(See Chromatography á621ñ, System Suitability.) Relative standard deviation: NMT 3.0% for the triethyl
Mode: GC aconitate peak, Standard solution A; NMT 3.0% for the
Detector: Flame ionization triethyl citrate peak, Standard solution B; NMT 3.0% for
Column: 0.32-mm × 30-m; 0.5-µm layer of phase G42 the acetyltriethyl citrate peak, Standard solution C
Temperatures Analysis
Injector: 225° Samples: Standard solution A, Standard solution B, Standard
Detector: 275° solution C, and Sample solution
Column: See Table 1. [NOTE—See Table 2 for the relative retention times.]

Table 1 Table 2
Hold Time Compound Name Relative Retention Time
Initial Temperature Final at Final
Temperature Ramp Temperature Temperature Ethanol 0.11
(°) (°/min) (°) (min)
Ethyl acetate 0.16
50 — 50 5
Triethyl aconitatea 0.93
50 20 220 15
Triethyl citrate 0.95

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Printed on: Thu Feb 09 2023, 01:02:09 AM(EST) Status: Not Yet Official on 09-Feb-2023 DocId: GUID-4CF097A8-66E5-4CE8-919D-669B5EEB1541_5_en-US
Printed by: Dang Van Vu Official Date: 01-May-2023 Document Type: NF @2023 USPC
Do Not Distribute DOI Ref: j8h8u DOI: https://doi.org/10.31003/USPNF_M675_05_01
2

Table 2 (continued) Triethyl citrate: NMT 0.3%

Compound Name Relative Retention Time Individual impurity: NMT 0.3%
Total impurities: NMT 1%▲ (NF 1-May-2023)
Triethyl isocitrate 0.97
SPECIFIC TESTS
Acetyltriethyl citrate 1.0

Any unidentified impurity — Delete the following:

a Triethyl (E)-prop-1-ene-1,2,3-tricarboxylate.
▲
• SPECIFIC GRAVITY á841ñ▲ (NF 1-May-2023)

Calculate the percentage of triethyl aconitate or triethyl Delete the following:

citrate in the portion of Acetyltriethyl Citrate taken: ▲
• REFRACTIVE INDEX á831ñ▲ (NF 1-May-2023)
Result = (rU/rS) × (CS/CU) × 100

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Change to read:
rU = peak area of triethyl aconitate or triethyl citrate
from the Sample solution • ACIDITY
rS = peak area of triethyl aconitate or triethyl citrate
▲
Neutralized isopropyl alcohol: To a suitable quantity of
from Standard solution A or Standard solution B, isopropyl alcohol add 2–3 drops of bromothymol blue TS

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respectively and just sufficient 0.10 N sodium hydroxide dropwise to
CS = concentration of USP Triethyl Aconitate RS or USP produce a faint blue color. [NOTE—Prepare Neutralized
Triethyl Citrate RS in Standard solution A or isopropyl alcohol just prior to use.]▲ (NF 1-May-2023)
Standard solution B, respectively (mg/mL) Sample ▲solution:▲ (NF 1-May-2023) 32.0 g ▲of Triethyl Citrate
CU = concentration of Acetyltriethyl Citrate in the in 30 mL of Neutralized isopropyl alcohol▲ (NF 1-May-2023)

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Sample solution (mg/mL) Analysis: ▲▲ (NF 1-May-2023)Add bromothymol blue TS, and
titrate with 0.10 N sodium hydroxide to a faint blue
Calculate the percentage of each individual impurity, endpoint.
excluding any solvent peaks, in the portion of Acceptance criteria: NMT 1.0 mL of 0.10 N sodium
Acetyltriethyl Citrate taken: hydroxide is required.
• WATER DETERMINATION á921ñ, Method I: NMT 0.3%
Result = (rU/rS) × (CS/CU) × 100
O
ADDITIONAL REQUIREMENTS
rU = peak area of each individual impurity from the • PACKAGING AND STORAGE: Preserve in tight containers.
Sample solution
rS = peak area of acetyltriethyl citrate from Standard Change to read:
solution C • USP REFERENCE STANDARDS á11ñ
CS = concentration of USP Acetyltriethyl Citrate RS in USP Acetyltriethyl Citrate RS
e
Standard solution C (mg/mL) ▲
USP Triethyl Aconitate RS▲ (NF 1-May-2023)
CU = concentration of Acetyltriethyl Citrate in the
USP Triethyl Citrate RS
Sample solution (mg/mL)
B

Acceptance criteria
Triethyl aconitate: NMT 0.5%
To

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