bp & usp monographs of isoniazid
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British Pharmacopoeia Volume I & II
Monographs: Medicinal and Pharmaceutical
Substances
Isoniazid
General Notices
(Ph. Eur. monograph 0146)
C6H7N3O 137.1 54-85-3
Action and use
Antituberculosis drug.
Preparations
Isoniazid Injection
Isoniazid Oral Solution
Isoniazid Tablets
Ph Eur
DEFINITION
Isoniazid contains not less than 99.0 per cent and not more than the equivalent of 101.0 per cent
of pyridine-4-carbohydrazide, calculated with reference to the dried substance.
CHARACTERS
A white or almost white, crystalline powder or colourless crystals, freely soluble in water, sparingly
soluble in alcohol.
IDENTIFICATION
First identification A, B.
Second identification A, C.
A. Melting point ( 2.2.14 ) : 170 °C to 174 °C.
B. Examine by infrared absorption spectrophotometry ( 2.2.24 ) , comparing with the spectrum
obtained with isoniazid CRS.
C. Dissolve 0.1 g in 2 mL of water R and add 10 mL of a warm 10 g/L solution of vanillin R. Allow
to stand and scratch the wall of the test tube with a glass rod. A yellow precipitate is formed,
which, after recrystallisation from 5 mL of alcohol (70 per cent V/V) R and drying at 100 °C to
105 °C, melts ( 2.2.14 ) at 226 °C to 231 °C.
TESTS
Solution S
Dissolve 2.5 g in carbon dioxide-free water R and dilute to 50 mL with the same solvent.
Appearance of solution
Solution S is clear ( 2.2.1 ) and not more intensely coloured than reference solution BY7 (2.2.2,
Method II).
pH ( 2.2.3 )
The pH of solution S is 6.0 to 8.0.
Hydrazine and related substances
Examine by thin-layer chromatography ( 2.2.27 ) , using silica gel GF254 R as the coating substance.
Test solution Dissolve 1.0 g of the substance to be examined in a mixture of equal volumes of
acetone R and water R and dilute to 10.0 mL with the same mixture of solvents.
Reference solution Dissolve 50.0 mg of hydrazine sulfate R in 50 mL of water R and dilute to
100.0 mL with acetone R. To 10.0 mL of this solution add 0.2 mL of the test solution and dilute to
100.0 mL with a mixture of equal volumes of acetone R and water R.
Apply separately to the plate 5 µL of each solution and develop over a path of 15 cm using a
mixture of 10 volumes of water R, 20 volumes of acetone R, 20 volumes of methanol R and 50
volumes of ethyl acetate R. Allow the plate to dry in air and examine in ultraviolet light at 254 nm.
Any spot in the chromatogram obtained with the test solution, apart from the principal spot, is not
more intense than the spot in the chromatogram obtained with the reference solution (0.2 per
cent). Spray the plate with dimethylaminobenzaldehyde solution R1. Examine in daylight. An
additional spot, corresponding to hydrazine, appears in the chromatogram obtained with the
reference solution. Any corresponding spot in the chromatogram obtained with the test solution is
not more intense than the spot corresponding to hydrazine in the chromatogram obtained with the
reference solution (0.05 per cent).
Heavy metals ( 2.4.8 )
2.0 g complies with limit test C for heavy metals (10 ppm). Prepare the standard using 2 mL of
lead standard solution (10 ppm Pb) R.
Loss on drying ( 2.2.32 )
Not more than 0.5 per cent, determined on 1.00 g by drying in an oven at 105 °C.
Sulfated ash ( 2.4.14 )
Not more than 0.1 per cent, determined on 1.0 g.
ASSAY
Dissolve 0.250 g in water R and dilute to 100.0 mL with the same solvent. To 20.0 mL of the
solution add 100 mL of water R, 20 mL of hydrochloric acid R, 0.2 g of potassium bromide R and
0.05 mL of methyl red solution R. Titrate dropwise with 0.0167 M potassium bromate, shaking
continuously, until the red colour disappears.
1 mL of 0.0167 M potassium bromate is equivalent to 3.429 mg of C6H7N3O.
British Pharmacopoeia Volume III
Formulated Preparations: Specific Monographs
Isoniazid Tablets
General Notices
Action and use
Antituberculosis drug.
DEFINITION
Isoniazid Tablets contain Isoniazid.
The tablets comply with the requirements stated under Tablets and with the following
requirements.
Content of isoniazid, C6H7N3O
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Shake a quantity of the powdered tablets containing 0.1 g of Isoniazid with 10 mL of ethanol (96%)
for 15 minutes, centrifuge and decant the supernatant liquid. Extract the residue with two further
10-mL quantities of ethanol (96%) and evaporate the combined extracts to dryness. The infrared
absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of
isoniazid (RS 196).
TEST
Dissolution
Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test
for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 1, rotating the basket at 100 revolutions per minute.
(b) Use 900 mL of water, at a temperature of 37°, as the medium.
PROCEDURE
After 45 minutes withdraw a 10 mL sample of the medium and measure the absorbance of the
filtered sample, suitably diluted if necessary, at the maximum at 263 nm, Appendix II B.
DETERMINATION OF CONTENT
Calculate the total content of isoniazid, C6H7N3O, in the medium taking 307 as the value of A(1%,
1 cm) at the maximum at 263 nm.
ASSAY
Weigh and powder 20 tablets. Dissolve a quantity of the powder containing 150 mg of Isoniazid as
completely as possible in water, filter and wash the residue with sufficient water to produce
250 mL. To 50 mL of the resulting solution add 50 mL of water, 20 mL of hydrochloric acid and
0.2 g of potassium bromide and titrate with 0.0167M potassium bromate VS determining the end
point electrometrically. Each mL of 0.0167M potassium bromate VS is equivalent to 3.429 mg of
C6H7N3O.
STORAGE
Isoniazid Tablets should be protected from light.
USP monographs
Isoniazid
(eye'' soe nye' a zid).
C6H7N3O 137.14
4-Pyridinecarboxylic acid, hydrazide.
Isonicotinic acid hydrazide [54-85-3].
» Isoniazid contains not less than 98.0 percent and not more than 102.0 percent of C6H7N3O,
calculated on the dried basis.
Packaging and storage—Preserve in tight, light-resistant containers. Store at 25 , excursions
permitted between 15 and 30 .
USP REFERENCE STANDARDS 11 —
USP Isoniazid RS
Identification—
A: Infrared Absorption 197K .
B: Transfer about 50 mg of it to a 500-mL volumetric flask, add water to volume, and mix. Transfer
10.0 mL of the resulting solution to a 100-mL volumetric flask, add 2.0 mL of 0.1 N hydrochloric
acid, dilute with water to volume, and mix to obtain a 1 in 100,000 solution: the UV absorption
spectrum of the solution so obtained exhibits maxima and minima only at the same wavelengths
as that of a similar solution of USP Isoniazid RS, concomitantly measured.
MELTING RANGE 741 : between 170 and 173 .
PH 791 : between 6.0 and 7.5, in a solution (1 in 10).
LOSS ON DRYING 731 —Dry it at 105 for 4 hours: it loses not more than 1.0% of its weight.
RESIDUE ON IGNITION 281 : not more than 0.2%.
HEAVY METALS, Method II 231 : 0.002%.
Assay—
Mobile phase—Dissolve 4.4 g of docusate sodium in 600 mL of methanol, add 400 mL of water,
adjust with 2 N sulfuric acid to a pH of 2.5, and mix. Make adjustments if necessary (see System
Suitability under Chromatography 621 ).
Standard preparation—Dissolve an accurately weighed quantity of USP Isoniazid RS in Mobile
phase, and quantitatively dilute with Mobile phase to obtain a solution having a known
concentration of about 0.32 mg per mL.
Assay preparation—Transfer about 16 mg of Isoniazid, accurately weighed, to a 50-mL volumetric
flask, dissolve in and dilute with Mobile phase to volume, and mix.
Chromatographic system (see CHROMATOGRAPHY 621 )—The liquid chromatograph is equipped
with a 254-nm detector and a 4.6-mm × 25-cm column that contains packing L1. The flow rate is
about 1.5 mL per minute. Chromatograph the Standard preparation, and record the peak
responses as directed for Procedure: the column efficiency determined from the isoniazid peak is
not less than 1800 theoretical plates; the tailing factor for the isoniazid peak is not more than 2.0;
and the relative standard deviation for replicate injections 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 measure the
responses for the major peaks. Calculate the quantity, in mg, of C6H7N3O in the portion of Isoniazid
taken by the formula:
50C(rU / rS)
in which C is the concentration, in mg per mL, of USP Isoniazid RS in the Standard preparation;
and rU and rS are the peak responses of isoniazid obtained from the Assay preparation and the
Standard preparation, respectively.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Behnam Davani, Ph.D., M.B.A. Senior Scientific Liaison1-301-816-8394
(SM12010) Monographs - Small Molecules 1
Reference Standards
RS Technical Services1-301-816-8129rstech@usp.org
USP34–NF29 Page 3203
Pharmacopeial Forum: Volume No. 29(6) Page 1912
Chromatographic Column—
ISONIAZID
Chromatographic columns text is not derived from, and not part of, USP 34 or NF 29.
Isoniazid Tablets
» Isoniazid Tablets contain not less than 90.0 percent and not more than 110.0 percent of the
labeled amount of isoniazid (C6H7N3O).
Packaging and storage—Preserve in well-closed, light-resistant containers.
USP REFERENCE STANDARDS 11 —
USP Isoniazid RS
Identification—
A: The retention time of the isoniazid peak in the chromatogram of the Assay preparation
corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
B: Transfer a portion of finely powdered Tablets, equivalent to about 50 mg of isoniazid, to a 500-
mL volumetric flask. Add water to volume, mix, and filter a portion of the mixture. Proceed as
directed in Identification test B under Isoniazid, beginning with “Transfer 10.0 mL of the resulting
solution to a 100-mL volumetric flask.”
DISSOLUTION 711 —
Medium: 0.01 N hydrochloric acid; 900 mL.
Apparatus 1: 100 rpm.
Time: 45 minutes.
Procedure—Determine the amount of C6H7N3O dissolved by employing UV absorption at the
wavelength of maximum absorbance at about 263 nm on filtered portions of the solution under
test, suitably diluted with Dissolution Medium, in comparison with a Standard solution having a
known concentration of USP Isoniazid RS in the same Medium.
Tolerances—Not less than 80% (Q) of the labeled amount of C6H7N3O is dissolved in 45 minutes.
UNIFORMITY OF DOSAGE UNITS 905 : meet the requirements.
Procedure for content uniformity—Transfer 1 finely powdered Tablet to a 500-mL volumetric flask
with the aid of 200 mL of water. Shake by mechanical means for 30 minutes, add water to volume,
and mix. Filter, and discard the first 20 mL of the filtrate. Dilute a portion of the filtrate quantitatively
and stepwise, if necessary, with a 3 in 100 mixture of 0.1 N hydrochloric acid and water to obtain a
solution containing about 10 µg per mL. Dissolve an accurately weighed quantity of USP Isoniazid
RS in a volume of water corresponding to that used to dissolve a similar amount of isoniazid from
the Tablet, and dilute quantitatively and stepwise, if necessary, with a 3 in 100 mixture of 0.1 N
hydrochloric acid and water to obtain a Standard solution having a known concentration of about
10 µg per mL. Concomitantly determine the absorbances of both solutions in 1-cm cells at the
wavelength of maximum absorbance at about 263 nm, with a suitable spectrophotometer, using
water as the blank. Calculate the quantity, in mg, of isoniazid (C6H7N3O) in the Tablet taken by the
formula:
(TC / D)(AU / AS)
in which T is the labeled quantity, in mg, of isoniazid in the Tablet; C is the concentration, in µg per
mL, of USP Isoniazid RS in the Standard solution; D is the concentration, in µg per mL, of
isoniazid in the solution from the Tablet, based on the labeled quantity per Tablet and the extent of
dilution; and AU and AS are the absorbances of the solution from the Tablet and the Standard
solution, respectively.
Assay—
Buffer solution—Prepare a 0.1 M monobasic potassium phosphate solution, adjust with 10 N
sodium hydroxide to a pH of 6.9, add sufficient triethanolamine to obtain a solution having a known
concentration of 0.2 mM of triethanolamine, and mix.
Mobile phase—Prepare a filtered and degassed mixture of Buffer solution and methanol (95:5).
Make adjustments if necessary (see System Suitability under Chromatography 621 ).
Standard preparation—Dissolve an accurately weighed quantity of USP Isoniazid RS in Mobile
phase, and dilute quantitatively, and stepwise, if necessary, with Mobile phase to obtain a solution
having a known concentration of about 0.32 mg per mL.
Assay preparation—Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately
weighed portion of the powder, equivalent to 32 mg of isoniazid, to a 100-mL volumetric flask, add
40 mL of Mobile phase, and sonicate for 10 minutes. Cool to room temperature, dilute with Mobile
phase to volume, and centrifuge for 5 minutes.
Chromatographic system (see Chromatography 621 )—The liquid chromatograph is equipped
with a 254-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is
about 1.5 mL per minute. Chromatograph the Standard preparation, and record the peak
responses as directed for Procedure: the capacity factor, k¢, is not less than 2.35; the column
efficiency is not less than 1800 theoretical plates; the tailing factor is not more than 1.5; and the
relative standard deviation for replicate injections is not more than 1.0%.
Procedure—Separately inject equal volumes (about 20 µL) of the Standard preparation and the
Assay preparation into the chromatograph, record the chromatograms, and measure the
responses for the major peaks. Calculate the quantity, in mg, of isoniazid (C6H7N3O) in the portion
of Tablets taken by the formula:
100C(rU / rS)
in which C is the concentration, in mg per mL, of USP Isoniazid RS in the Standard preparation;
and rU and rS are the peak responses obtained from the Assay preparation and the Standard
preparation, respectively.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Behnam Davani, Ph.D., M.B.A.
(SM12010) Monographs - Small Molecules 1
Topic/Question Contact Expert Committee
Senior Scientific Liaison1-301-816-8394
Reference Standards
RS Technical Services1-301-816-8129rstech@usp.org
711 Margareth R.C. Marques, Ph.D. Senior Scientific Liaison1-301-816-8106
(GCDF2010) General Chapters - Dosage Forms
USP34–NF29 Page 3204
Chromatographic Column—
ISONIAZID TABLETS
Chromatographic columns text is not derived from, and not part of, USP 34 or NF 29.
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