Accessed from 202.150.141.
30 by merck1 on Mon Aug 06 05:18:27 EDT 2018
2266 Isoproterenol / Official Monographs
Assay preparation—Transfer an accurately measured vol-
ume of Inhalation Solution, equivalent to about 25 mg of
isoproterenol sulfate, to a 100-mL volumetric flask, add
50.0 mL of 0.30 N acetic acid, dilute with water to volume,
and mix.
Chromatographic system—Proceed as directed in the As-
say under Isoproterenol Hydrochloride.
Procedure—Proceed as directed for Procedure in the Assay
under Isoproterenol Hydrochloride. Calculate the quantity, in
mg, of (C11H17NO3)2 · H2SO4 in each mL of the Inhalation
Solution taken by the formula:
(260.30/247.72)(0.1)(C/V)(hU / hS)
in which 260.30 is one-half of the molecular weight of an-
hydrous isoproterenol sulfate; 247.72 is the molecular
weight of isoproterenol hydrochloride; V is the volume, in
mL, of Inhalation Solution taken; and C, hU, and hS are as
defined therein.
Isosorbide Concentrate
.
C6H10O4 146.14
D-Glucitol, 1,4:3,6-dianhydro-.
1,4:3,6-Dianhydro-D-glucitol [652-67-5].
» Isosorbide Concentrate is an aqueous solution
containing, in each 100 g, not less than 70.0 g
USP Monographs
and not more than 80.0 g of C6H10O4.
Packaging and storage—Preserve in tight, light-resistant
containers.
Labeling—The label states that this article is not intended
for direct administration to humans or animals.
USP Reference standards 〈11〉—
USP Isosorbide RS
Identification—[NOTE—Isosorbide is hygroscopic. Take pre-
cautions to protect isolated isosorbide crystals from atmos-
pheric moisture.]
A: Dry a portion of it in an evaporating dish over phos-
phorus pentoxide at 70° and at a pressure of 50 mm of
mercury for 48 hours, changing the phosphorus pentoxide
after 24 hours. Scratch the bottom of the dish with a glass
rod or seed with a crystal of isosorbide, if necessary, to initi-
ate crystallization: the crystals so obtained melt between 60°
and 63° when tested by the procedure for Class I substances
(see Melting Range or Temperature 〈741〉).
B: The IR absorption spectrum of a potassium bromide
dispersion of the crystals obtained as directed in Identifica-
tion test A exhibits maxima and minima only at the same
wavelengths as that of a similar preparation of USP
Isosorbide RS.
Specific rotation 〈781S〉: between +44.5° and +47.0°.
Test solution: 80 mg of isosorbide per mL, in water.
Water Determination, Method I 〈921〉: between 24.0%
and 26.0%.
Residue on ignition 〈281〉: not more than 0.01%.
Delete the following:
•Heavy metals, Method II 〈231〉:
. not more than 5 ppm,
calculated on the anhydrous basis.• (Official 1-Jan-2018)
Official from August 1, 2018
Copyright (c) 2018 The United States Pharmacopeial Convention. All rights reserved.
USP 41
Periodate consumption—Dilute about 15 g, accurately
weighed, with 25 mL of water, and add 50.0 mL of a solu-
tion prepared by dissolving 5.4 g of periodic acid in 100 mL
of water and adding 1900 mL of glacial acetic acid. Allow to
stand for 1 hour. Add 20 mL of potassium iodide TS, and
titrate with 0.1 N sodium thiosulfate VS to the disappear-
ance of the brown color. Add 3 mL of starch TS, and com-
plete the titration. Perform a blank determination, and note
the difference in volumes required. If the volume required
for the specimen is less than 0.8 of that required for the
blank, repeat the procedure with a smaller specimen. The
difference in volume corresponds to not more than 0.20 mL
of 0.1 N sodium thiosulfate for each g of Concentrate
taken.
Acid value—Dilute about 15 g, accurately weighed, with
50 mL of water, and titrate with 0.02 N potassium hydrox-
ide VS to a phenolphthalein endpoint. Perform a blank de-
termination, and make any necessary correction. Calculate
the acid value taken by the formula:
56.11(AN / W)
in which A is the number of mL of potassium hydroxide VS
consumed; N is its normality; and W is the weight, in g, of
Concentrate taken. The limit is 0.5, calculated on the anhy-
drous basis.
Methyl ethyl ketone—
Internal standard solution—Prepare a solution in water
containing about 1 mg per mL of methyl isobutyl ketone.
Standard preparation—Prepare a solution in water con-
taining an accurately known concentration of methyl ethyl
ketone equivalent to about 1 mg per mL. Pipet 5 mL of this
solution into a 100-mL volumetric flask, add 5.0 mL of Inter-
nal standard solution, add water to volume, and mix.
Test preparation—Pipet 5 mL of Internal standard solution
into a 100-mL volumetric flask, add Concentrate to volume,
and mix.
Support—Place about 90 g of unsilanized support S1A in
a crystallizing dish, and cover it with chloroform. Stir the
mixture thoroughly, and carefully remove the supernatant
chloroform with an aspirator. Spread the moist support on a
clean surface, and allow it to air-dry. Place the dried support
in the crystallizing dish, and cover it with 0.5 N alcoholic
potassium hydroxide TS. Allow it to stand for one-half hour
with occasional stirring. Carefully pour off the supernatant
alcoholic potassium hydroxide solution, and wash the moist
support with water until the washing is neutral to phenol-
phthalein indicator. Spread the moist support on a clean
surface, and allow it to air-dry.
Chromatographic system—The gas chromatograph is
equipped with a flame-ionization detector and a 0.6-m ×
2-mm column packed with 25% liquid phase G16 on unsi-
lanized acid- and base-washed Support which has been
washed with chloroform, and conditioned as directed (see
Chromatography 〈621〉). The column is maintained at 70°,
and nitrogen is used as the carrier gas at a flow rate of
about 30 mL per minute. In a suitable chromatogram, the
relative standard deviation of five replicate injections is not
more than 3.0%, and the resolution is not less than 2.0.
Procedure—Inject about 3 µL of the Standard preparation
into the gas chromatograph, record the chromatogram, and
measure the peak response of each component. [NOTE—
Clean the syringe after each injection with pentane. Do not
use acetone.] Similarly inject about 3 µL of the Test prepara-
tion, record the chromatogram, and measure the peak re-
sponse of each component. Calculate the quantity, in mg,
of methyl ethyl ketone in each mL of the Concentrate taken
by the formula:
(1 / 0.95)C(RU / RS)
in which C is the concentration, in mg per mL, of methyl
ethyl ketone in the Standard preparation, and RU and RS are
Accessed from 202.150.141.30 by merck1 on Mon Aug 06 05:18:27 EDT 2018
USP 41
the ratios of the response of the methyl ethyl ketone to the
response of the internal standard obtained from the Test
preparation and the Standard preparation, respectively. The
limit is 0.05 mg per mL.
Assay—
Internal standard solution—Dissolve a suitable quantity of
triethylene glycol in water to obtain a solution containing
about 15 mg per mL.
Standard solution—Prepare a solution of USP Isosorbide
RS in water containing an accurately known concentration
equivalent to about 25 mg of C6H10O4 per mL.
Standard preparations—Pipet 2-, 3-, 4-, and 5-mL quanti-
ties of Standard solution into separate 50-mL volumetric
flasks, add 5.0 mL of Internal standard solution to each, add
water to volume, and mix.
Assay preparation—Transfer about 200 mg of Concen-
trate, accurately weighed, to a 100-mL volumetric flask, add
10.0 mL of Internal standard solution, add water to volume,
and mix.
Chromatographic system—The gas chromatograph is
equipped with a flame-ionization detector and a 3-mm ×
0.6-m glass column packed with support S9. The column is
maintained at 230°, and nitrogen is used as the carrier gas.
The retention time of the isosorbide peak is about 1.5, rela-
tive to that of triethylene glycol.
System suitability and standard curve—Inject 1-µL portions
of each Standard preparation, and record each peak re-
sponse. Plot the ratio of the peak response of isosorbide to
that of triethylene glycol versus the concentration, in mg
per mL, of isosorbide in the respective Standard preparation.
The analytical system is suitable for conducting the assay if
the correlation coefficient for the Standard curve is greater
than 0.980, the resolution, R, is not less than 1.5, and
neither tailing factor exceeds 2.0.
Procedure—Inject a 1-µL portion of the Assay preparation,
record the peak responses for the two major peaks, calculate
the ratio of the peak responses, and determine the concen-
tration, C, in mg per mL, of isosorbide in the Assay prepara-
tion by reference to the Standard curve. Calculate the quan-
tity, in mg, of C6H10O4 in the Concentrate taken by the
formula:
100C.
Isosorbide Oral Solution
.
» Isosorbide Oral Solution contains not less than
90.0 percent and not more than 110.0 percent of
the labeled amount of isosorbide (C6H10O4).
Packaging and storage—Preserve in tight containers.
USP Reference standards 〈11〉—
USP Isosorbide RS
Identification—The retention time of the major peak in
the chromatogram of the Assay preparation corresponds to
that in the chromatograms of the Standard preparations, as
obtained in the Assay.
Uniformity of dosage units 〈905〉—
FOR ORAL SOLUTION PACKAGED IN SINGLE-UNIT CONTAINERS:
meets the requirements.
Deliverable volume 〈698〉—
FOR ORAL SOLUTION PACKAGED IN MULTIPLE-UNIT CONTAINERS:
meets the requirements.
Official from August 1, 2018
Copyright (c) 2018 The United States Pharmacopeial Convention. All rights reserved.
Official Monographs / Isosorbide 2267
pH 〈791〉: between 3.2 and 3.8.
Assay—
Internal standard solution, Standard solution, Standard
preparations, Chromatographic system, and System suitability
and standard curve—Proceed as directed in the Assay under
Isosorbide Concentrate.
Assay preparation—Transfer an accurately measured vol-
ume of Oral Solution, equivalent to about 450 mg of
isosorbide, to a 250-mL volumetric flask, add 25.0 mL of
Internal standard solution, then add water to volume, and
mix.
Procedure—Proceed as directed for Procedure in the Assay
under Isosorbide Concentrate. Calculate the quantity, in mg,
of isosorbide (C6H10O4) in each mL of the Oral Solution
taken by the formula:
250(C/V)
in which C is the concentration, in mg per mL, of isosorbide
in the Assay preparation found by reference to the Standard
curve; and V is the volume, in mL, of Oral Solution taken.
.
Diluted Isosorbide Dinitrate
C6H8N2O8 236.14
D-Glucitol, 1,4:3,6-dianhydro-, dinitrate;
1,4:3,6-Dianhydro-D-glucitol dinitrate [87-33-2].
USP Monographs
DEFINITION
Diluted Isosorbide Dinitrate is a dry mixture of isosorbide
dinitrate (C6H8N2O8) with Lactose, Mannitol, or suitable
inert excipients to permit safe handling. It may contain up
to 1.0% of a suitable stabilizer, such as Ammonium Phos-
phate. It contains NLT 95.0% and NMT 105.0% of the
labeled amount of isosorbide dinitrate (C6H8N2O8). It usu-
ally contains approximately 25% of isosorbide dinitrate.
[CAUTION—Exercise proper precautions in handling undiluted
isosorbide dinitrate, which is a powerful explosive and can
be exploded by percussion or excessive heat. Only ex-
ceedingly small amounts should be isolated.]
IDENTIFICATION
Change to read:
• ▲
. A.▲USP41
Sample solution: Transfer to a medium-porosity,
sintered-glass filtering crucible a quantity of Diluted
Isosorbide Dinitrate, equivalent to about 50 mg of
isosorbide dinitrate, and pass three 5-mL portions of ac-
etone through it. Evaporate the combined extracts at a
temperature not exceeding 35°, with the aid of a gen-
tle current of air, and dry the residue under vacuum
over calcium chloride at room temperature for 16 h.
Prepare a solution (1 in 40) of the residue so obtained,
in chloroform.
Standard solution: A similar preparation from the resi-
due obtained from USP Diluted Isosorbide Dinitrate RS
Acceptance criteria: The IR absorption spectrum of the
Sample solution, determined in a 0.1-mm cell, exhibits
maxima only at the same wavelengths as that of the
Standard solution.