Accessed from 10.6.1.1 by correct6 on Mon May 25 16:37:49 EDT 2015
6760 Methylene / Official Monographs
NF 33
DEFINITION
Methylparaben contains NLT 98.0% and NMT 102.0% of
C8H8O3.
Calculate the percentage of methylene chloride
(CH2Cl2) in the portion of sample taken:
Result = (rU/rT) × 100
IDENTIFICATION
• A. INFRARED ABSORPTION 〈197M〉
• B. MELTING RANGE OR TEMPERATURE 〈741〉: 125°–128°
rU
= peak response of methylene chloride
rT
= sum of all the peak responses
Acceptance criteria: NLT 99.0%
IMPURITIES
• LIMIT OF NONVOLATILE RESIDUE
Sample: 50 g
Analysis: Evaporate the Sample in a platinum or porcelain dish on a steam bath, and dry at 105° for 30 min.
Acceptance criteria: NMT 0.002%; NMT 1 mg of
residue
Delete the following:
•• HEAVY METALS, Method I 〈231〉
.
NF Monographs
Test preparation: 15 mL (20 g)
Analysis: Evaporate the Test preparation in a glass evaporating dish on a steam bath to dryness. Cool, add
2 mL of hydrochloric acid, and slowly evaporate again
on a steam bath to dryness. Dissolve the residue in
1 mL of 1 N acetic acid, and add 24 mL of water.
Acceptance criteria: NMT 1 µg/g• (Official 1-Dec-2015)
SPECIFIC TESTS
• LIMIT OF HYDROGEN CHLORIDE
Sample: 20.0 mL
Analysis: Into each of two glass-stoppered, 50-mL
color-comparison cylinders having an internal diameter
of 20 mm, place 10 mL of water, 2 drops of phenolphthalein TS, and sufficient 0.010 N sodium hydroxide
to produce a pink color that persists after vigorous
shaking for 30 s and is of equal intensity in each cylinder.
[NOTE—In the following step, take special care to avoid
contamination with carbon dioxide.]
Into one of the cylinders, place the Sample and 0.70 mL
of 0.010 N sodium hydroxide, and shake again.
Acceptance criteria: NMT 0.001%; the pink color in
the sample cylinder is at least as intense as that in the
comparison cylinder, and the color persists for NLT 15
min.
• SPECIFIC GRAVITY 〈841〉: 1.318–1.322
• WATER DETERMINATION, Method I 〈921〉: NMT 0.02%
• FREE CHLORINE
Sample: 10 mL
Analysis: To the Sample add 10 mL of water and 0.1 mL
of potassium iodide TS, shake for 2 min, and allow the
liquids to separate.
Acceptance criteria: The lower layer does not show a
violet tint.
ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in tight containers.
.
Methylparaben
C8H8O3
Benzoic acid, 4-hydroxy-, methyl ester;
Methyl p-hydroxybenzoate [99-76-3].
152.15
ASSAY
• PROCEDURE
Mobile phase, Sample solution, Standard solution B,
and Chromatographic system: Proceed as described
in the procedure for Related Substances.
System suitability
Sample: Standard solution B
Suitability requirements
Relative standard deviation: NMT 0.85% for 6
injections
Analysis
Samples: Sample solution and Standard solution B
Calculate the percentage of Methylparaben in the Sample solution:
Result = P × (rU × CS)/(rS × CU)
P
= labeled purity of USP Methylparaben RS
expressed as a percentage
rU
= peak area of methylparaben from the Sample
solution
CS
= concentration of methylparaben in Standard
solution B
rS
= peak area of methylparaben from Standard
solution B
CU
= concentration of Methylparaben in the Sample
solution
Acceptance criteria: 98.0%–102.0%
IMPURITIES
Inorganic Impurities
• RESIDUE ON IGNITION 〈281〉: NMT 0.1%, determined on
1.0 g
Organic Impurities
• PROCEDURE: RELATED SUBSTANCES
Mobile phase: Methanol and a 6.8 g/L solution of potassium dihydrogen phosphate (65:35 v/v)
Sample solution: Dissolve 50.0 mg of Methylparaben
in 2.5 mL of methanol, and dilute with Mobile phase to
50.0 mL. Dilute 10.0 mL of this solution with Mobile
phase to 100.0 mL.
Standard solution A: 5.0 µg/mL each of p-hydroxybenzoic acid and USP Methylparaben RS in Mobile
phase
Standard solution B: Dissolve 50.0 mg of USP Methylparaben RS in 2.5 mL of methanol, and dilute with Mobile phase to 50.0 mL. Dilute 10.0 mL of this solution
with Mobile phase to 100.0 mL.
Standard solution C: Dilute 1.0 mL of the Sample solution with Mobile phase to 20.0 mL. Dilute 1.0 mL of this
solution with Mobile phase to 10.0 mL.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 272 nm
Column: 4.6-mm × 15-cm; 5-µm packing L1
Flow rate: 1.3 mL/min
Injection size: 10 µL
Run time: About 5 times the retention time of
methylparaben
System suitability
Sample: Standard solution A
[NOTE—The retention time of methylparaben is about
2.3 min; the relative retention time for p-hydroxybenzoic acid is about 0.6.]
Suitability requirements
Resolution: NLT 2.0 between the p-hydroxybenzoic
acid and methylparaben peaks
Official from May 1, 2015
Copyright (c) 2015 The United States Pharmacopeial Convention. All rights reserved.
Accessed from 10.6.1.1 by correct6 on Mon May 25 16:37:49 EDT 2015
NF 33
Official Monographs / Methylparaben 6761
Analysis
Samples: Sample solution and Standard solution C
[NOTE—Disregard any limit that is 0.2 times the area
of the principal peak in the chromatogram obtained
with Standard solution C (0.1%).]
Acceptance criteria
p-Hydroxybenzoic acid: The peak area in the Sample
solution, multiplied by 1.4 to correct for the calculation of content, is NMT the area of the principal peak
in Standard solution C (0.5%).
Unspecified impurities: The peak area of each impurity in the Sample solution is NMT the area of the
principal peak in Standard solution C (0.5%).
Total impurities: The total peak area for all impurities
in the Sample solution is NMT twice the area of the
principal peak in Standard solution C (1.0%).
SPECIFIC TESTS
• COLOR OF SOLUTION
Sample solution: 100 mg/mL in alcohol
Comparison solution: Mix 2.4 mL of ferric chloride CS,
1.0 mL of cobaltous chloride CS, and 0.4 mL of cupric
sulfate CS with 0.3 N hydrochloric acid to make 10 mL.
Dilute 5 mL of this solution with 0.3 N hydrochloric
acid to make 100 mL. [NOTE—Prepare and use this solution immediately.]
Analysis
Samples: Alcohol, Sample solution, and Comparison
solution
Make the comparison by viewing the solutions downward in matched color-comparison tubes against a
white surface (see Color and Achromicity 〈631〉).
Acceptance criteria: The Sample solution is clear and
not more intensely colored than alcohol or the Comparison solution.
• ACIDITY
Sample solution: To 2 mL of the Sample solution prepared in the test for Color of Solution, add 3 mL of alcohol, 5 mL of carbon dioxide-free water, and 0.1 mL of
bromocresol green TS.
Analysis: Titrate with 0.10 N sodium hydroxide.
Acceptance criteria: NMT 0.1 mL is required to produce a blue color.
ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in well-closed
containers.
• USP REFERENCE STANDARDS 〈11〉
USP Methylparaben RS
Methylparaben Sodium
C8H7NaO3
174.13
Benzoic acid, 4-hydroxy-, methyl ester, sodium salt;
Methyl p-hydroxybenzoate, sodium salt;
Sodium 4-methoxycarbonylphenolate [5026-62-0].
DEFINITION
Methylparaben Sodium contains NLT 95.0% and NMT
102.0% of methylparaben sodium (C8H7NaO3), calculated
on the anhydrous basis.
ASSAY
• PROCEDURE
Mobile phase: Methanol and a 6.8 g/L solution of potassium dihydrogen phosphate (65:35, v/v)
System suitability solution: 5.0 µg/mL each of p-hydroxybenzoic acid and USP Methylparaben RS in Mobile
phase
Standard solution: Dissolve 50.0 mg of USP Methylparaben RS in 2.5 mL of methanol, and dilute with Mobile
phase to 50.0 mL. Dilute 10.0 mL of this solution with
Mobile phase to 100.0 mL.
Sample solution: Dissolve 50.0 mg of Methylparaben
Sodium in 2.5 mL of methanol, and dilute with Mobile
phase to 50.0 mL. Dilute 10.0 mL of this solution with
Mobile phase to 100.0 mL.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 272 nm
Column: 4.6-mm × 15-cm; 5-µm packing L1
Flow rate: 1.3 mL/min
Injection volume: 10 µL
Run time: About 5 times the retention time of the
methylparaben peak
System suitability
Samples: System suitability solution and Standard
solution
[NOTE—The retention time for methylparaben is about
2.2 min; the relative retention times for p-hydroxybenzoic acid and methylparaben are about 0.7 and 1.0,
respectively.]
Suitability requirements
Resolution: NLT 2.0 between the p-hydroxybenzoic
acid and methylparaben peaks, System suitability
solution
Relative standard deviation: NMT 0.85% for six injections, Standard solution
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of methylparaben sodium
(C8H7NaO3) in the portion of Methylparaben Sodium
taken:
Result = P × (rU/rS) × (CS/CU) × (Mr1/Mr2)
P
rU
rS
CS
CU
= labeled purity of USP Methylparaben RS
expressed as a percentage
= peak area of methylparaben from the Sample
solution
= peak area of methylparaben from the Standard
solution
= concentration of methylparaben in the
Standard solution
= concentration of Methylparaben Sodium in
the Sample solution
Official from May 1, 2015
Copyright (c) 2015 The United States Pharmacopeial Convention. All rights reserved.
NF Monographs
.
IDENTIFICATION
• A.
Standard: 0.5 g of USP Methylparaben RS
Sample: 0.5 g
Analysis: Dissolve the Sample in 5 mL of water. Acidify
with hydrochloric acid, and filter the resulting precipitate. Wash the precipitate with water, and dry it over
silica gel for 5 h. Repeat with the Standard.
Acceptance criteria: The IR absorption spectrum of a
mineral oil dispersion of the Sample exhibits maxima
only at the same wavelengths as those of a similar
preparation of the Standard.
• B.
Sample solution: Ignite 0.3 g of Methylparaben Sodium, cool, and dissolve the residue in about 3 mL of
3 N hydrochloric acid.
Acceptance criteria: A platinum wire dipped in the
Sample solution imparts an intense, persistent yellow
color to a nonluminous flame.