Printed on: Wed Feb 08 2023, 11:58:02 PM(EST) Status: Currently Official on 09-Feb-2023 DocId: GUID-81E046F1-D3BE-49C5-B216-BCA4E55F6E78_5_en-US
Printed by: Dang Van Vu Official Date: Official as of 01-Dec-2021 Document Type: USP & NF @2023 USPC
Do Not Distribute DOI Ref: 8vnv1 DOI: https://doi.org/10.31003/USPNF_M1238_05_01
1
Linear velocity: 35 cm/s
Alcohol Carrier gas: Helium
Portions of this monograph that are national USP text, and are Injection volume: 1.0 µL
not part of the harmonized text, are marked with symbols System suitability
(◆◆) to specify this fact. Sample: Standard solution B
Suitability requirements
Resolution: NLT 1.5 between the first major peak
(acetaldehyde) and the second major peak (methanol)
C2H6O 46.07 Analysis
Ethanol; Samples: Sample solution A, Sample solution B, Standard
Ethyl alcohol CAS RN®: 64-17-5. solution A, Standard solution B, Standard solution C, and
DEFINITION Standard solution D
◆
Alcohol contains NLT 92.3% and NMT 93.8%, by weight, Methanol calculation
◆
corresponding to NLT 94.9% and NMT 96.0%, by volume, [NOTE—To be performed as a part of Identification C.] ◆
at 15.56°, of ethanol (C2H5OH).◆
Result = (rU/rS)
IDENTIFICATION
• A. It meets the requirements of the test for Specific Gravity rU = peak area of methanol from Sample solution A
á841ñ. rS = peak area of methanol from Standard solution A
• B. SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared
Spectroscopy: 197F or 197S: Neat Acetaldehyde calculation (sum of acetaldehyde and
• ◆C. LIMIT OF METHANOL acetal)
al
[NOTE—This test must be performed to be in compliance
with USP, in addition to Identification A and B above.] Result = {[AE/(AT − AE)] × CA} + {[DE/(DT − DE)] × CD × (Mr1/
Sample solution A, Standard solution A, Standard Mr2)}
solution B, Chromatographic system, and System
suitability: Proceed as directed in Organic Impurities. AE = peak area of acetaldehyde from Sample solution A
Analysis: Proceed as directed in the Organic Impurities test, AT = peak area of acetaldehyde from Standard
Methanol calculation.
Acceptance criteria: Meets the requirements in Table 2 for
methanol.◆
ci CA
solution B
= concentration of acetaldehyde in Standard
solution B (µL/L)
DE = peak area of acetal from Sample solution A
IMPURITIES DT = peak area of acetal from Standard solution C
ffi
• LIMIT OF NONVOLATILE RESIDUE
CD = concentration of acetal in Standard solution C (µL/
Sample: 100 mL of Alcohol
L)
Analysis: Evaporate the Sample in a tared dish on a water
Mr1 = molecular weight of acetaldehyde, 44.05
bath, and dry at 100°–105° for 1 h.
Acceptance criteria: The weight of the residue is NMT Mr2 = molecular weight of acetal, 118.2
2.5 mg.
Benzene calculation
O
• ORGANIC IMPURITIES
Sample solution A: Alcohol (substance under test)
Result = [BE/(BT − BE)] × CB
Sample solution B: 300 µL/L of 4-methylpentan-2-ol in
Sample solution A BE = peak area of benzene from Sample solution A
Standard solution A: 200 µL/L of methanol in Sample
solution A BT = peak area of benzene from Standard solution D
◆
[NOTE—To be prepared for use in Identification C] ◆ CB = concentration of benzene in Standard solution D
Standard solution B: 10 µL/L each of methanol and (µL/L)
acetaldehyde in Sample solution A
[NOTE—If necessary, the identity of benzene can be
Standard solution C: 30 µL/L of acetal in Sample solution A
confirmed using another suitable chromatographic
Standard solution D: 2 µL/L of benzene in Sample solution A
system (stationary phase with a different polarity).]
Chromatographic system
Any other impurity calculation
(See Chromatography á621ñ, System Suitability.)
Mode: GC Result = (rU/rM) × CM
Detector: Flame ionization
Column: 0.32-mm × 30-m fused-silica capillary; bonded rU = peak area of each impurity in Sample solution B
with a 1.8-µm layer of phase G43 rM = peak area of 4-methylpentan-2-ol in Sample
Injection type: Split; split ratio 20:1 solution B
Temperatures CM = concentration of 4-methylpentan-2-ol in Sample
Injection port: 200° solution B (µL/L)
Detector: 280°
Column: See Table 1. Acceptance criteria: See Table 2.
Table 1 Table 2
Initial Tempera- Tempera- Final Tempera- Hold Time at Fi- Name Acceptance Criteria
ture ture Ramp ture nal Temperature
(°) (°/min) (°) (min) Methanol NMT 0.5, corresponding to 200 µL/L
40 0 40 12 NMT 10 µL/L, expressed as acetalde-
Acetaldehyde and acetal hyde
40 10 240 10
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Printed on: Wed Feb 08 2023, 11:58:02 PM(EST) Status: Currently Official on 09-Feb-2023 DocId: GUID-81E046F1-D3BE-49C5-B216-BCA4E55F6E78_5_en-US
Printed by: Dang Van Vu Official Date: Official as of 01-Dec-2021 Document Type: USP & NF @2023 USPC
Do Not Distribute DOI Ref: 8vnv1 DOI: https://doi.org/10.31003/USPNF_M1238_05_01
2
Table 2 (continued) Transfer a sufficient portion of Sample solution A and Sample
Name Acceptance Criteria solution B to separate test tubes of colorless, transparent,
neutral glass with a flat base and an internal diameter of
Benzene NMT 2 µL/L 15–25 mm to obtain a depth of 40 mm. Similarly transfer
Sum of all other impuritiesa NMT 300 µL/L portions of Standard suspension A, Standard suspension B,
and Blank to separate matching test tubes. Compare the
a Disregard any peaks of less than 9 µL/L (0.03 times the area of the peak Samples in diffused daylight, viewing vertically against a
corresponding to 4-methylpentan-2-ol in Sample solution B). black background (see Visual Comparison á630ñ). The
diffusion of light must be such that Standard suspension A
SPECIFIC TESTS can readily be distinguished from water, and Standard
suspension B can readily be distinguished from Standard
Change to read:
suspension A.
• ◆SPECIFIC GRAVITY á841ñ: 0.812–0.816 at 15.56°, Acceptance criteria: Sample solution A and Sample solution
indicating 92.3%–93.8%, by weight, or 94.9%–96.0%, by B show the same clarity as that of water or their opalescence
volume, of ethanol (C2H5OH) is not more pronounced than that of Standard suspension
▲
[NOTE—In the event that a temperature of 15.56° A.◆
cannot be reached, the Alcoholometric Table found in • ACIDITY OR ALKALINITY
the Reagents and Reference Tables section of USP-NF Phenolphthalein solution: Dissolve 0.1 g of
can be used to provide the conversion factors needed phenolphthalein in 80 mL of alcohol, and dilute with water
to complete this test at other to 100 mL.
temperatures.◆]▲ (USP 1-Dec-2021) Sample: 20 mL of Alcohol
• ULTRAVIOLET ABSORPTION Analysis: To the Sample add 20 mL of freshly boiled and
al
Analytical wavelength: 235–340 nm cooled water and 0.1 mL of Phenolphthalein solution. The
Cell: 5 cm solution is colorless. Add 1.0 mL of 0.01 N sodium
Reference: Water hydroxide.
Acceptance criteria Acceptance criteria: The solution is pink (30 µL/L,
Absorbance: NMT 0.40 at 240 nm; NMT 0.30 between expressed as acetic acid).
• ◆COLOR OF SOLUTION
250 nm and 260 nm; NMT 0.10 between 270 nm and
340 nm
Curve: The spectrum shows a steadily descending curve
with no observable peaks or shoulders.
ci Standard stock solution: Combine 3.0 mL of ferric chloride
CS, 3.0 mL of cobaltous chloride CS, 2.4 mL of cupric
sulfate CS, and 1.6 mL of dilute hydrochloric acid (10 mg/
• ◆CLARITY OF SOLUTION mL).
[NOTE—Compare each Sample solution to Standard Standard solution: Transfer 1.0 mL of Standard stock
ffi
suspension A and to water in diffused daylight 5 min solution to a 100-mL volumetric flask, and dilute with dilute
after preparation of Standard suspension A.] hydrochloric acid (10 mg/mL). Prepare the Standard
Hydrazine solution: 10 mg/mL of hydrazine sulfate in solution immediately before use.
water. Allow to stand for 4–6 h. Sample solution: Substance under test
Methenamine solution: Transfer 2.5 g of methenamine Blank: Water
to a 100-mL glass-stopper flask, add 25.0 mL of water, Analysis
O
insert the glass stopper, and mix to dissolve. Samples: Standard solution, Sample solution, and Blank
Primary opalescence suspension: Transfer 25.0 mL of Transfer a sufficient portion of the Sample solution to a test
Hydrazine solution to the Methenamine solution in the tube of colorless, transparent, neutral glass with a flat base
100-mL glass-stopper flask. Mix, and allow to stand for and an internal diameter of 15–25 mm to obtain a depth
24 h. This suspension is stable for 2 months, provided it is of 40 mm. Similarly transfer portions of the Standard
stored in a glass container free from surface defects. The solution and Blank to separate, matching test tubes.
suspension must not adhere to the glass and must be well Compare the Samples in diffused daylight, viewing
mixed before use. vertically against a white background (see Visual
Opalescence standard: Transfer 15.0 mL of the Primary Comparison á630ñ).
opalescence suspension to a 1000-mL volumetric flask, and Acceptance criteria: The Sample solution has the
dilute with water to volume. This suspension should not be appearance of water or is not more intensely colored than
used beyond 24 h after preparation. the Standard solution.◆
Standard suspension A: Opalescence standard and water ADDITIONAL REQUIREMENTS
(1 in 20) • PACKAGING AND STORAGE: Preserve in tight containers,
Standard suspension B: Opalescence standard and water protected from light.
(1 in 10) • USP REFERENCE STANDARDS á11ñ
Sample solution A: Substance to be examined USP Alcohol RS
Sample solution B: Dilute 1.0 mL of Sample solution A with
water to 20 mL, and allow to stand for 5 min before testing.
Blank: Water
Analysis
Samples: Standard suspension A, Standard suspension B,
Sample solution A, Sample solution B, and Blank
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