Acyclovir for Injection

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Acyclovir for Injection contains NLT 90.0% and NMT 110.0% of the labeled amount of acyclovir (C₈H₁₁N₅O₃).

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 Procedure

Mobile phase: 0.02 M acetic acid

System suitability solution A: 0.1 mg/mL each of USP Acyclovir RS and guanine in 0.1 N sodium hydroxide

System suitability solution B: 2.0 μg/mL of guanine in 0.1 N sodium hydroxide

Standard solution: 0.1 mg/mL of USP Acyclovir RS in 0.1 N sodium hydroxide

Sample solution: Nominally 0.1 mg/mL of acyclovir prepared as follows. Constitute 1 vial of Acyclovir for Injection with water. Transfer an amount, equivalent to 10 mg of acyclovir, to a 100-mL volumetric flask, and dilute with water to volume.

Chromatographic system

Mode: LC

Detector: UV 254 nm

Column: 4.2-mm × 25-cm; packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 μL

System suitability

Samples: System suitability solution A and System suitability solution B

[Note - The relative retention times for guanine and acyclovir are 0.6 and 1.0, respectively, in System suitability solution A.]

Suitability requirements

Resolution: NLT 2.0 between guanine and acyclovir, System suitability solution A

Relative standard deviation: NMT 2.0% for the acyclovir peak, System suitability solution A

Relative standard deviation: NMT 2.0%, System suitability solution B

Analysis

Calculate the percentage of acyclovir (C₈H₁₁N₅O₃) in the portion of Acyclovir for Injection taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of the Sample solution

r_s = peak response of the Standard solution

C_s = concentration of USP Acyclovir RS in the Standard solution (mg/mL)

C_u = concentration of the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

Change to read:

4.1 Procedure

Solution A: 0.17 M acetic acid and methanol (125:8)

Solution B: Methanol

Mobile phase: See Table 1.

System suitability solution: 0.5 μg/mL each of purine and USP Acyclovir RS in Solution A

Acyclovir standard solution: 5 μg/mL of USP Acyclovir RS in Solution A

Guanine solution: 0.05 mg/mL of guanine prepared as follows. Dissolve 25 mg of guanine in 50 mL of 0.1 N sodium hydroxide in a 500-mL volumetric flask, and bring the solution to volume with water.

Standard solution A: 0.5 μg/mL of USP Acyclovir RS from (ERR 1-Apr-2022) Acyclovir standard solution in Solution A

Standard solution B: 5 μg/mL of guanine from (ERR 1-Apr-2022) Guanine solution in Solution A

Sample solution: Equivalent to 0.5 mg/mL of acyclovir from a mixture of NLT 10 reconstituted vials of Acyclovir for Injection in Solution A

4.2 Chromatographic system

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 25-cm; packing L1

Flow rate: 1 mL/min

Injection volume: 50 μL

4.3 System suitability

Samples: System suitability solution, Standard solution A, and Standard solution B

[Note - Typical retention times for guanine and acyclovir of Standard solution A and Standard solution B are 5.8 and 14 min, respectively.]

4.4 Suitability requirements

Resolution: NLT 2.0 between purine and acyclovir, System suitability solution

Relative standard deviation: NMT 1% for the acyclovir and the guanine peaks, Standard solution A and Standard solution B

4.5 Analysis 1

Calculate the percentage of guanine in the Acyclovir for Injection taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response for guanine, if present, in the Sample solution

r_s = peak response of guanine in Standard solution B (ERR 1-Apr-2022)

C_s = concentration of guanine in Standard solution B (ERR 1-Apr-2022) (mg/mL)

C_u = nominal concentration of acyclovir in the Sample solution (mg/mL)

Acceptance criteria 1: NMT 1.0% guanine

4.6 Analysis 2

Calculate the percentage of each other impurity in the portion of Acyclovir for Injection taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response for each impurity

r_s= peak response of acyclovir in Standard solution A (ERR 1-Apr-2022)

C_s = concentration of USP Acyclovir RS in Standard solution A (ERR 1-Apr-2022) (mg/mL)

C_u = nominal concentration of acyclovir in the Sample solution (mg/mL)

Acceptance criteria 2: NMT 0.15% for any peak having a relative retention time of about 0.7 compared to the acyclovir peak; NMT 0.5% for any other individual impurity; and NMT 1.0% for the total of all other impurities

5 SPECIFIC TESTS

pH 〈791〉: 11.0–12.5, 50 mg/mL of acyclovir

Water Determination, Method I 〈921〉: NMT 5.5%

Sterility Tests 〈71〉: Meets the requirements

Uniformity of Dosage Units 〈905〉: Meets the requirements

Bacterial Endotoxins Test 〈85〉: NMT 0.174 USP Endotoxin Unit/mg of acyclovir

Other Requirements: Meets the requirements for labeling in Labeling 〈7〉, Labels and Labeling for Injectable Products

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store between 15° and 25°. Protect from light.

USP Reference Standards 〈11〉

USP Acyclovir RS