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Printed by: Le Tran Official Date: Official as of 01-May-2020 Document Type: DIETARY SUPPLEMENTS @2021 USPC
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IMPURITIES
Alpha Lipoic Acid • RESIDUE ON IGNITION á281ñ: Less than 0.1%
• CHROMATOGRAPHIC PURITY, PROCEDURE 1
Buffer solution, Mobile phase, Standard solution, Sample
solution, and Chromatographic system: Proceed as
directed in the Assay.
Diluted standard solution: Dilute the Standard solution
(1 in 1000) with Mobile phase.
System suitability
Sample: Diluted standard solution
Suitability requirements
C8H14O2S2 206.33
Signal-to-noise ratio: NLT 10
Thioctic acid; Relative standard deviation: NMT 10.0%
1,2-Dithiolane-3-pentanoic acid; Analysis
1,2-Dithiolane-3-valeric acid [1077-28-7]. Sample: Sample solution
DEFINITION Calculate the percentage of each impurity in the portion of
Alpha Lipoic Acid contains NLT 99.0% and NMT 101.0% Alpha Lipoic Acid taken:
of C8H14O2S2, calculated on the dried basis.
Result = (r U/r T) × 100
IDENTIFICATION
• A. The retention time of the peak for alpha lipoic acid of the rU = peak response of each individual impurity from
Sample solution corresponds to that of the Standard the Sample solution
solution, as obtained in the Assay. rT = sum of the responses of all the peaks from the

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Sample solution
Change to read:
Acceptance criteria
• B. ▲SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared Individual impurities: NMT 0.1%
Spectroscopy: 197K▲ (CN 1-May-2020) Total impurities: NMT 2.0%
ASSAY
• PROCEDURE
Buffer solution: 0.68 g/L of monobasic potassium
ci • CHROMATOGRAPHIC PURITY, PROCEDURE 2
[NOTE—Use low-actinic glassware.]
Standard solution A: 40.0 mg/mL of USP Alpha Lipoic
Acid RS in dimethylformamide
phosphate Standard solution B: 20.0 mg/mL of USP Alpha Lipoic
Mobile phase: Methanol, Buffer solution, and acetonitrile
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Acid RS in dimethylformamide, prepared from the
(58:46:9). Adjust with phosphoric acid solution (8.3 in 100) dilution of Standard solution A
to a pH of 3.0–3.1. Standard solution C: 10.0 mg/mL of USP Alpha Lipoic
Standard solution: 1.0 mg/mL of USP Alpha Lipoic Acid RS Acid RS in dimethylformamide, prepared from the
in Mobile phase dilution of Standard solution B
Sample solution: 1.0 mg/mL of Alpha Lipoic Acid in Mobile Sample solution: 40.0 mg/mL of Alpha Lipoic Acid in
phase
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dimethylformamide
Chromatographic system Chromatographic system
(See Chromatography á621ñ, System Suitability.) (See Chromatography á621ñ, Thin-Layer Chromatography.)
Mode: LC Mode: TLC
Detector: UV 215 nm Adsorbent: 0.25-mm layer of chromatographic silica gel
Column: 4.6-mm × 250-mm; packing L1 mixture
Column temperature: 35° Application volume: 5 µL
Flow rate: 1.2 mL/min Developing solvent system: n-Propyl alcohol, ethyl
Injection size: 20 µL acetate, water, and 25% ammonia water (40:40:10:5).
System suitability Allow the chamber to become saturated for at least 1 h.
Sample: Standard solution Iodine vapor–saturated chamber: Transfer 4 g of iodine
Suitability requirements crystals to a small watch glass, and place in a
Column efficiency: NLT 10,000 theoretical plates chromatographic chamber. Allow the chamber to
Tailing factor: NMT 2.0 for the alpha lipoic acid peak become saturated for at least 2 h.
Relative standard deviation: NMT 2.0% for alpha Analysis
lipoic acid Samples: Standard solution A, Standard solution B, Standard
Analysis solution C, and Sample solution
Samples: Standard solution and Sample solution Proceed as directed in the chapter, except to develop until
Calculate the percentage of alpha lipoic acid (C8H14O2S2) in the solvent front has moved 10 cm. Remove the plate, and
the portion of Alpha Lipoic Acid taken: allow to air-dry until the ammonia disappears completely.
Heat at 50° for 20 min, cool the plate, and place in the
Result = (r U/r S) × (C S/C U) × 100 Iodine vapor–saturated chamber until the spots are visible.
The R F value for the alpha lipoic acid spot is 0.25–0.30 and
rU = peak response from the Sample solution
for the polymeric lipoic acid spot is 0.
rS = peak response from the Standard solution Acceptance criteria: No spot other than the alpha lipoic
CS = concentration of USP Alpha Lipoic Acid RS in the acid spot from the Sample solution is more intense than the
Standard solution (mg/mL) spot at R F = 0 from Standard solution A.
CU = concentration of Alpha Lipoic Acid in the
Sample solution (mg/mL) SPECIFIC TESTS
• MELTING RANGE OR TEMPERATURE á741ñ: 60.0°–62.0°
Acceptance criteria: 99.0%–101.0% on the dried basis

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Printed on: Sun Aug 08 2021, 03:39:17 AM Official Status: Currently Official on 08-Aug-2021 DocId: 1_GUID-714C3E1B-39DF-4C9D-BEEF-CF0C988B0688_4_en-US
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Printed by: Le Tran Official Date: Official as of 01-May-2020 Document Type: DIETARY SUPPLEMENTS @2021 USPC
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• OPTICAL ROTATION, Specific Rotation á781Sñ ADDITIONAL REQUIREMENTS

Sample solution: 50 mg/mL of Alpha Lipoic Acid, in • PACKAGING AND STORAGE: Preserve in well-closed
dehydrated alcohol containers.
Acceptance criteria: –1.0° to +1.0° • USP REFERENCE STANDARDS á11ñ
• LOSS ON DRYING á731ñ: Dry a sample in vacuum at 40° for USP Alpha Lipoic Acid RS
3 h: it loses NMT 0.2% of its weight.

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