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NORFLOXACIN

Category Antibacterial.

      Norfloxacin contains not less than 99.0 per cent and not more than 101.0 per cent of C16H18FN3O3, calculated on the dried basis.

Description White to pale yellow, crystalline powder.

Solubility Slightly soluble in water, in acetone and in ethanol; freely soluble in acetic acid; sparingly soluble in chloroform; very slightly soluble in methanol and in ethyl acetate; insoluble in ether.

Stability It is sensitive to light and moisture.

Contra-indication It is contra-indicated in patients with hypersensitivity to quinolone derivatives, with a history of tendinitis or tendon rupture with norfloxacin or any quinolone and during the first trimester of pregnancy, nursing mothers and infants under 3 months.

Warning

      1. It should be used with caution in patients with known or suspected CNS disorders (e.g., severe cerebral arterosclerosis, seizure disorders), hepatic or renal function impairment.

      2. It may cause nausea, vomiting, fever, headache, drowsiness, malaise, vertigo, visual disturbances, abdominal pain, cholestasis, thrombocytopenia, leukopenia, hemolytic anemia, prolonged QT interval,asthenia, myalgia, arthropathy, myasthenia gravis exacerbation, tendinitis and tendon rupture, angio-edema, allergic skin reactions, photosensitivity, toxic epidermal necrolysis, exfoliative dermatitis, vasculitis, erythema multiform and Stevens-Johnson Syndrome.

      3. Caution should be exercised if it is to be used concomitantly with antacids containing magnesium, aluminium or calcium; oral multivitamin and mineral supplements containing divalent or trivalent cations; probenecid; theophylline, caffeine-containing products; sucralfate; oral anticoagulants and drugs that prolong QT interval.

      4. Risk-benefit should be considered if it is to be used in prepubertal children and pregnant women during the second and third trimesters.

Precaution

      1. Periodic determinations of hepatic, renal and hematopoietic functions are recommended during prolonged therapy.

      2. Patients should be cautioned to avoid unnecessary exposure to direct sunlight.

      3. Patients who become drowsy when taking this medicine should be cautioned against engaging in activities requiring alertness and skill such as driving a car or operating hazardous machinery or appliances.

      4. Patients should be advised to discontinue the drug and inform their physician if they experience pain, swelling, inflammation or rupture of a tendon and to rest and refrain from exercise.

      5. Careful monitoring of the patient and periodic in vitro susceptibility tests are essential to protect superinfection. 

Additional information

      1. Patients should be instructed to drink sufficient quantities of fluids to ensure proper hydration and adequate urinary output during therapy.

      2. Cross-resistance occurs among the fluoroquinolones.

Packaging and storage Norfloxacin shall be kept in tightly closed containers, protected from light.

Labelling The label on the container states storage condition.

Identification

      A. The infrared absorption spectrum is concordant with the spectrum obtained from Norfloxacin RS (Appendix 2.1) or with the reference spectrum of Norfloxacin.

      B. The ultraviolet absorption spectrum of a 0.0005 per cent w/v in 0.1 M sodium hydroxide exhibits a maximum and a minimum at the same wavelengths as that of a similar solution of Norfloxacin RS, concomitantly measured, and the respective absorptivities at about 273 nm, calculated on the dried basis, do not differ by more than 3 per cent. (Note Use low-actinic glassware.)

Loss on drying Not more than 1.0 per cent w/w after drying at 100º at a pressure not exceeding 0.7 kPa (about 5 Torr) to constant weight (Appendix 4.15).

Sulfated ash Not more than 0.10 per cent w/w (Appendix 5.3), determined in a platinum crucible.

Heavy metals Not more than 15 ppm (Method II, Appendix 5.2). Use 2.0 g; for the Standard Preparation, use 3 ml of lead standard solution (10 ppm Pb).

Chromatographic purity Carry out the test as described in the “Thin-layer Chromatography” (Appendix 3.1), using precoated high-performance thin-layer chromatographic silica gel GF254 plate (0.25-mm layer) as the stationary phase and a mixture of 40 volumes of chloroform, 40 volumes of methanol, 20 volumes of toluene, 14 volumes of diethylamine and 8 volumes of water as the mobile phase.

      Test solution Dissolve a quantity of the test substance in a mixture of 1 volume of methanol and 1 volume of dichloromethane to obtain a test solution containing 8.0 mg per ml.

      Comparison solution A Dissolve 4.0 mg of Norfloxacin RS in 1 ml of glacial acetic acid, add 4 ml of methanol, and mix. To 1 ml of this Standard stock solution add 9 ml of the mixture of 1 volume of methanol and 1 volume of dichloromethane to obtain Comparison solution A.

      Comparison solution B Dilute a portion of Comparison solution A with an equal volume of the mixture of 1 volume of methanol and 1 volume of dichloromethane to obtain Comparison solution B.

      Procedure Apply separately to the plate, previously washed with methanol and air-dried, 5 μl of Test solution, 1, 1.5 and 2 μl of Comparison solution A and 5 μl of Comparison solution B. The spots of Comparison solutions A and B are equivalent to 0.2, 0.3, 0.4, and 0.5 per cent of impurities, respectively. Allow the solvent front to move about nine-tenths of the length of the plate. After removal of the plate, allow it to dry in air. Examine under ultraviolet light (254 and 366 nm). Compare the intensities of any secondary spots observed in the chromatogram of the Test solution with those of the principal spots in the chromatograms of the Comparison solutions A and B: the sum of the intensities of secondary spots obtained from the Test solution corresponds to not more than 0.5 per cent of impurities. 

Assay Dissolve about 460 mg of Norfloxacin, accurately weighed, in 100 ml of anhydrous glacial acetic acid. Titrate with 0.1 M perchloric acid VS, determining the end-point potentiometrically (Appendix 6.1). Perform a blank determination, and make any necessary correction. Each ml of 0.1 M perchloric acid is equivalent to 31.93 mg of C16H18FN3O3.

MONOGRAPHS • NORFLOXACIN
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หมายเหตุ / Note : TP II 2011 PAGE 133-134