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Category Antiviral.

          Acyclovir contains not less than 98.0 per cent and not more than 101.0 per cent of C₈H₁₁N₅O₃, calculated on the anhydrous basis.

Description White to off-white, crystalline powder.

Solubility Slightly soluble in water; soluble in dilute hydrochloric acid; insoluble in ethanol.

Warning
          1. Dose reduction may be required in acute or chronic renal impairment.
          2. It may cause renal impairment, increased serum bilirubin and liver enzymes, gastro-intestinal disturbance, neuropsychiatric toxicity and hair loss.
          3. Concurrent use with nephrotoxic medications may increase the potential for nephrotoxicity, especially in the presence of renal function impairment.
          4. Risk-benefit should be considered if it is to be used in pregnant or nursing women.

          Precaution Periodic determinations of blood urea nitrogen and serum creatinine are recommended.

Additional information
          1. Acyclovir tablets may be taken with meals since absorption has not been shown to be significantly affected by food; however, they may be taken on an empty stomach.
          2. Intermittent short-term treatment of recurrent herpes genitalis infections may be effective for some patients, especially when treatment is patient-initiated during the prodrome or first sign of lesion formation.
          3. Patients allergic to ganciclovir may also be allergic to acyclovir because of the chemical similarity of the two medications.
          4. Use of acyclovir has not been shown to prevent the transmission of herpes simplex virus to sexual partners.
          5. Herpes genitalis may be sexually transmitted even if the partner is asymptomatic.

          Packaging and storage Acyclovir shall be kept in tightly closed containers.

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

Water Not more than 6.0 per cent w/w (Karl Fischer Method, Appendix 4.12).

Limit for guanine Not more than 0.7 per cent w/w, using the chromatogram from the Assay. Calculate the quantity, in μg, of guanine in the portion of Acyclovir taken from the peak corresponding to the peak of Guanine standard preparation.

Assay Carry out the determination as described in the “High-pressure Liquid Chromatography” (Appendix 3.5).

          Mobile phase Prepare a 0.1 per cent v/v solution of glacial acetic acid. Make adjustments if necessary.

          System suitability solution 1 Dissolve accurately weighed quantities of Acyclovir RS and guanine in 0.1 M sodium hydroxide, and dilute quantitatively, and stepwise if necessary, with water to obtain a solution having known concentrations of about 100 μg of each per ml.

          System suitability solution 2 Dissolve an accurately weighed quantity of guanine in 0.1 M sodium hydroxide, and dilute quantitatively, and stepwise if necessary, with water to obtain a solution having a known concentration of about 0.7 μg per ml.

          Guanine standard preparation Transfer about 8.75 mg of guanine, accurately weighed, to a 500-ml volumetric flask. Dissolve in 50 ml of 0.1 M sodium hydroxide, dilute with water to volume, and mix. Transfer 2.0 ml of this solution to a 50-ml volumetric flask, dilute with 0.01 M sodium hydroxide to volume, and mix to obtain a solution having a known concentration of about 0.7 μg per ml.

          Standard preparation Dissolve about 25 mg of Acyclovir RS, accurately weighed, in 5 ml of 0.1 M sodium hydroxide in a 50-ml volumetric flask, dilute with water to volume, and mix. Transfer 10.0 ml of this solution to a 50-ml volumetric flask, dilute with 0.01 M sodium hydroxide to volume, and mix to obtain a solution having a known concentration of about 100 μg of Acyclovir RS per ml.

          Assay preparation Dissolve about 100 mg of Acyclovir, accurately weighed, in 20 ml of 0.1 M sodium hydroxide in a 200-ml volumetric flask, dilute with water to volume, and mix. Transfer 10.0 ml of this solution to a 50-ml volumetric flask, dilute with 0.01 M sodium hydroxide to volume, and mix.

          Chromatographic system The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilane chemically bonded to porous silica or ceramic microparticles, (b) Mobile phase at a flow rate of about 3 ml per minute, and (c) an ultraviolet photometer set at 254 nm.

          To determine the suitability of the chromatographic system, chromatograph System suitability solution 1, System suitability solution 2, and record the peak responses
as directed under Procedure: the resolution factor between acyclovir and guanine is not less than 2.0, the symmetry factor for the analyte peak is not more than 2, and the relative standard deviation for replicate injections is not more than 2.0 per cent.

          Procedure Separately inject equal volumes (about 20 μl) of Standard preparation, Guanine standard preparation and Assay preparation into the chromatograph, record the chromatograms, and measure the responses for all the peaks.

          Calculation Calculate the content of C₈H₁₁N₅O₃ in the Acyclovir taken, using the declared content of C₈H₁₁N₅O₃ in Acyclovir RS.