Ganciclovir
(gan sye' kloe vir).
Click to View Image

C9H13N5O4 255.23
6H-Purin-6-one, 2-amino-1,9-dihydro-9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]-;    
9-[[2-Hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine     [82410-32-0].
DEFINITION
Ganciclovir contains NLT 98.0% and NMT 102.0% of C9H13N5O4, calculated on the anhydrous basis.
IDENTIFICATION
•  B. Ultraviolet Absorption 197U
Sample solution:  10 µg/mL in methanol
ASSAY
•  Procedure
Solution A:  Trifluoroacetic acid and water (0.5 in 1000)
Mobile phase:  Acetonitrile and Solution A (1:1)
System suitability solution:  0.1 mg/mL each of USP Ganciclovir RS and USP Ganciclovir Related Compound A RS in Mobile phase. [Note—Sonicate the solution if necessary. ]
Standard solution:  0.22 mg/mL of USP Ganciclovir RS in Mobile phase
Sample solution:  0.22 mg/mL of Ganciclovir in Mobile phase
Chromatographic system 
Mode:  LC
Detector:  UV 254 nm
Column:  4.6-mm × 25-cm; packing L9
Column temperature:  40
Flow rate:  1.5 mL/min
Injection size:  20 µL
System suitability 
Sample:  System suitability solution
[Note—The relative retention times for ganciclovir related compound A and ganciclovir are 0.9 and 1.0, respectively. ]
Suitability requirements 
Resolution:  NLT 1.4 between ganciclovir and ganciclovir related compound A
Column efficiency:  NLT 5000 theoretical plates
Tailing factor:  NMT 1.4
Relative standard deviation:  NMT 1.0%
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of C9H13N5O4 in the portion of Ganciclovir taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response from the Sample solution
rS== peak response from the Standard solution
CS== concentration of USP Ganciclovir RS in the Standard solution (mg/mL)
CU== concentration of Ganciclovir in the Sample solution (mg/mL)
Acceptance criteria:  98.0%–102.0% on the anhydrous basis
IMPURITIES
Inorganic Impurities 
•  Heavy Metals, Method II 231: NMT 20 ppm
•  Residue on Ignition 281: NMT 0.1%
Organic Impurities 
•  Procedure
Solution A, Mobile phase, System suitability solution, Chromatographic system, and System suitability:  Proceed as directed in the Assay.
Sample solution:  0.22 mg/mL of Ganciclovir in Mobile phase
Analysis 
Sample:  Sample solution
Calculate the percentage of each impurity in the portion of Ganciclovir taken:
Result = (rU/rT) × 100
rU== peak response for each impurity in the Sample solution
rT== sum of the responses of all the peaks
Acceptance criteria 
Ganciclovir related compound A:  NMT 0.5%
Total impurities:  NMT 1.5%
SPECIFIC TESTS
•  Water Determination, Method I 921: NMT 6.0%
[Note—Ganciclovir is extremely hygroscopic. ]
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in well-closed containers. Store at 25, excursions permitted between 15 and 30.
•  USP Reference Standards 11
USP Ganciclovir RS Click to View Structure
USP Ganciclovir Related Compound A RS
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 Liaison
1-301-816-8394
(SM12010) Monographs - Small Molecules 1
Reference Standards RS Technical Services
1-301-816-8129
rstech@usp.org
USP35–NF30 Page 3317
Pharmacopeial Forum: Volume No. 36(4) Page 923