Accessed from 10.6.1.
1 by merck1 on Mon May 11 20:36:48 EDT 2015
USP 38
Standard preparation, and record the peak responses as di-
rected for Procedure: the column efficiency is not less than
1500 theoretical plates; the tailing factor is not more than
2.5; and the relative standard deviation for replicate injec-
tions is not more than 2.0%.
Procedure—Separately inject equal volumes (about 10 µL)
of the Standard preparation and the Assay preparation into
the chromatograph, record the chromatograms, and meas-
ure the responses for the major peaks. Calculate the quan-
tity, in mg, of C18H28N2O4 · HCl in the portion of Acebutolol
Hydrochloride taken by the formula:
250C(rU / rS)
in which C is the concentration, in mg per mL, of USP
Acebutolol Hydrochloride RS in the Standard preparation;
and rU and rS are the acebutolol peak responses obtained
from the Assay preparation and the Standard preparation, re-
spectively.
Acebutolol Hydrochloride Capsules
.
» Acebutolol Hydrochloride Capsules contain the
equivalent of not less than 90.0 percent and not
more than 110.0 percent of the labeled amount
of acebutolol (C18H28N2O4).
Packaging and storage—Preserve in tight containers, and
store at controlled room temperature.
USP Reference standards 〈11〉—
USP Acebutolol Hydrochloride RS
Identification—The retention time of the major peak in
the chromatogram of the Assay preparation corresponds to
that in the chromatogram of the Standard preparation, as
obtained in the Assay.
Dissolution 〈711〉—
Medium: water; 900 mL.
Apparatus 2: 50 rpm.
Time: 30 minutes.
Procedure—Determine the amount of C18H28N2O4 dis-
solved by employing UV absorption at the wavelength of
maximum absorbance at about 232 nm on filtered portions
of the solution under test in comparison with a Standard
solution having a known concentration of USP Acebutolol
Hydrochloride RS in the same Medium.
Tolerances—Not less than 80% (Q) of the labeled amount
of acebutolol (C18H28N2O4) is dissolved in 30 minutes.
Uniformity of dosage units 〈905〉: meet the require-
ments.
Chromatographic purity—
TEST 1—
Buffer solution—Prepare as directed in the Assay.
Mobile phase—Prepare a filtered and degassed mixture of
Buffer solution and methanol (56:44). Make adjustments if
necessary (see System Suitability under Chromatography
〈621〉).
Diluent—Prepare a mixture of Buffer solution and metha-
nol (50:50).
Standard solution—Transfer about 30 mg of USP
Acebutolol Hydrochloride RS, accurately weighed, to a
50-mL volumetric flask. Add about 12 mL of methanol, swirl
to dissolve, dilute with Diluent to volume, and mix. Dilute
an accurately measured volume of this solution quantita-
tively, and stepwise if necessary, with Diluent to obtain a
solution having a known concentration of about 1.4 µg of
USP Acebutolol Hydrochloride RS per mL.
Official from May 1, 2015
Copyright (c) 2015 The United States Pharmacopeial Convention. All rights reserved.
Official Monographs / Acebutolol 2001
Test solution—Transfer an accurately weighed portion of
the contents of 20 opened Capsules, equivalent to about
250 mg of acebutolol, to a 100-mL volumetric flask, add
about 25 mL of methanol, and shake by mechanical means
for about 15 minutes. Dilute with Diluent to volume, and
mix. Centrifuge a portion of this solution, and transfer
10.0 mL of the clear supernatant to a 100-mL volumetric
flask. Dilute with Diluent to volume, and mix.
Chromatographic system (see Chromatography 〈621〉)—The
liquid chromatograph is equipped with a 240-nm detector
and a 3.9-mm × 15-cm column that contains 4-µm packing
L1. The flow rate is about 1 mL per minute. Chromatograph
the Standard solution, and record the peak responses as di-
rected for Procedure: the relative standard deviation for repli-
cate injections is not more than 6.0%.
Procedure—Separately inject equal volumes (about 35 µL)
of the Standard solution, Test solution, and Diluent into the
chromatograph, record the chromatograms for about two
times the retention time of acebutolol, and measure the re-
sponses for all the peaks, disregarding any peaks corre-
sponding to those obtained from the Diluent. Calculate the
percentage of each impurity eluting prior to the acebutolol
peak in the portion of Capsules taken by the formula:
(336.44/372.89)(0.4C)(ri / rS)
in which 336.44 and 372.89 are the molecular weights of
acebutolol and acebutolol hydrochloride, respectively; C is
the concentration, in µg per mL, of USP Acebutolol Hydro-
chloride RS in the Standard solution; ri is the peak response
of any individual impurity obtained from the Test solution;
and rS is the peak response of acebutolol obtained from the
Standard solution: not more than 0.5% of any individual im-
purity is found.
TEST 2—
Buffer solution—Prepare as directed in the Assay.
Mobile phase—Prepare a filtered and degassed mixture of
USP Monographs
Buffer solution and methanol (50:50). Make adjustments if
necessary (see System Suitability under Chromatography
〈621〉).
Standard solution—Transfer about 30 mg of USP
Acebutolol Hydrochloride RS, accurately weighed, to a
50-mL volumetric flask. Add about 12 mL of methanol, swirl
to dissolve, dilute with Mobile phase to volume, and mix.
Dilute an accurately measured volume of this stock solution
quantitatively, and stepwise if necessary, with Mobile phase
to obtain a solution having a known concentration of about
1.4 µg of USP Acebutolol Hydrochloride RS per mL.
Test solution—Transfer an accurately weighed portion of
the contents of 20 opened Capsules, equivalent to about
250 mg of acebutolol, to a 100-mL volumetric flask, add
about 25 mL of methanol, and shake by mechanical means
for about 15 minutes. Dilute with Mobile phase to volume,
and mix. Centrifuge a portion of this solution, and transfer
10.0 mL of the clear supernatant to a 100-mL volumetric
flask. Dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 〈621〉)—The
liquid chromatograph is equipped with a 240-nm detector
and a 3.9-mm × 15-cm column that contains 4-µm packing
L1. The flow rate is about 1 mL per minute. Chromatograph
the Standard solution, and record the peak responses as di-
rected for Procedure: the relative standard deviation for repli-
cate injections is not more than 6.0%.
Procedure—Separately inject equal volumes (about 70 µL)
of the Standard solution, Test solution, and Mobile phase into
the chromatograph, record the chromatograms for about
three times the retention time of acebutolol, and measure
the responses for all the peaks, disregarding any peaks cor-
responding to those obtained from the Mobile phase. Calcu-
late the percentage of each impurity eluting after the
 Accessed from 10.6.1.1 by merck1 on Mon May 11 20:36:48 EDT 2015
2002 Acebutolol / Official Monographs
acebutolol peak in the portion of Capsules taken by the
formula:
(336.44/372.89)(0.4C)(ri / rS)
in which 336.44 and 372.89 are the molecular weights of
acebutolol and acebutolol hydrochloride, respectively; C is
the concentration, in µg per mL, of USP Acebutolol Hydro-
chloride RS in the Standard solution; ri is the peak response
of any individual impurity obtained from the Test solution;
and rS is the peak response of acebutolol obtained from the
Standard solution: not more than 0.5% of any individual im-
purity is found. The sum of all individual impurities found in
Test 1 and Test 2 is not more than 1.0%.
Assay—
Buffer solution—Dissolve about 2.4 g of sodium 1-de-
canesulfonate in 1000 mL of water. Adjust with glacial acetic
acid to a pH of 3.5.
Mobile phase—Prepare a filtered and degassed mixture of
methanol and Buffer solution (60:40). Make adjustments if
necessary (see System Suitability under Chromatography
〈621〉).
Standard preparation—Dissolve an accurately weighed
quantity of USP Acebutolol Hydrochloride RS quantitatively
in methanol to obtain a solution having a known concentra-
tion of about 0.22 mg per mL. This is equivalent to about
0.2 mg of acebutolol per mL.
Assay preparation—Weigh and mix, as completely as pos-
sible, the contents of not fewer than 20 Capsules. Transfer
an accurately weighed portion of the powder, equivalent to
about 200 mg of acebutolol, to a 200-mL volumetric flask.
Add about 180 mL of methanol, and stir by mechanical
means for about 30 minutes. Dilute with methanol to vol-
ume, and mix. Transfer 5.0 mL of this solution to a 25-mL
volumetric flask, dilute with methanol to volume, and mix.
Chromatographic system (see Chromatography 〈621〉)—The
USP Monographs
liquid chromatograph is equipped with a 254-nm detector
and a 3.9-mm × 15-cm column that contains 5-µm packing
L1. The flow rate is about 1 mL per minute. Chromatograph
the Standard preparation, and record the peak responses as
directed for Procedure: the tailing factor is not more than
1.5; and the relative standard deviation for replicate injec-
tions is not more than 2.0%.
Procedure—Separately inject equal volumes (about 20 µL)
of the Standard preparation and the Assay preparation into
the chromatograph, record the chromatograms, and meas-
ure the responses for the major peaks. Calculate the quan-
tity, in mg, of acebutolol (C18H28N2O4) in the portion of
Capsules taken by the formula:
(336.44/372.89)(1000C)(rU / rS)
in which 336.44 and 372.89 are the molecular weights of
acebutolol and acebutolol hydrochloride, respectively; C is
the concentration, in mg per mL, of USP Acebutolol Hydro-
chloride RS in the Standard preparation; and rU and rS are
the acebutolol peak responses obtained from the Assay prep-
aration and the Standard preparation, respectively.
.
Acepromazine Maleate
C19H22N2OS · C4H4O4 442.53
Official from May 1, 2015
Copyright (c) 2015 The United States Pharmacopeial Convention. All rights reserved.
USP 38
Ethanone, 1-[10-[3-(dimethylamino)propyl]-10H-phe-
nothiazin-2-yl]-, (Z)-2-butenedioate (1:1);
10-[3-(Dimethylamino)propyl]phenothiazin-2-yl methyl ke-
tone maleate (1:1) [3598-37-6].
DEFINITION
Acepromazine Maleate contains NLT 98.0% and NMT
101.0% of acepromazine maleate (C19H22N2OS · C4H4O4),
calculated on the anhydrous basis.
Throughout the following procedures, protect samples, the
USP Reference Standard, and solutions containing them,
by conducting the procedures without delay, under sub-
dued light, or using low-actinic glassware.
IDENTIFICATION
• A. INFRARED ABSORPTION 〈197K〉
• B. The retention time of the major peak for
acepromazine of the Sample solution corresponds to that
of the Standard solution, as obtained in the Assay.
ASSAY
• PROCEDURE
Buffer: Add 6 mL of triethylamine to 700 mL of water,
and adjust with phosphoric acid to a pH of 2.5.
Mobile phase: Acetonitrile and Buffer (300:700)
Standard stock solution: 1 mg/mL of USP
Acepromazine Maleate RS in 0.05 N hydrochloric acid
Standard solution: 0.1 mg/mL of USP Acepromazine
Maleate RS in water from Standard stock solution
Sample stock solution: 1 mg/mL of Acepromazine
Maleate in 0.05 N hydrochloric acid
Sample solution: 0.1 mg/mL of Acepromazine Maleate
in water from Sample stock solution
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 280 nm
Column: 4-mm × 15-cm; 5-µm packing L7
Flow rate: 1 mL/min
Injection volume: 10 µL
System suitability
Sample: Standard solution
Suitability requirements
Column efficiency: NLT 1500 theoretical plates
Tailing factor: NMT 2.5
Relative standard deviation: NMT 2.0%
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of acepromazine maleate
(C19H22N2OS · C4H4O4) in the portion of Acepromazine
Maleate taken:
Result = (rU/rS) × (CS/CU) × 100
rU = peak area response from the Sample solution
rS = peak area response from the Standard solution
CS = concentration of USP Acepromazine Maleate
RS in the Standard solution (mg/mL)
CU = concentration of the Sample solution (mg/mL)
Acceptance criteria: 98.0%–101.0% on the anhydrous
basis
IMPURITIES
• RESIDUE ON IGNITION 〈281〉: NMT 0.2%
• ORGANIC IMPURITIES
Conduct this test without exposure to daylight, and with
the minimum necessary exposure to artificial light.
Diluent: Methanol and diethylamine (19:1)
Sample solution: 20.0 mg/mL of Acepromazine
Maleate in Diluent
Standard solution: 0.1 mg/mL of Acepromazine
Maleate in Diluent from the Sample solution