Zalcitabine is a synthetic nucleoside analogue and antiretroviral active pharmaceutical ingredient (API) belonging to the nucleoside reverse transcriptase inhibitor (NRTI) class. It is also known as 2',3'-Dideoxycytidine, Dideoxycytidine, and ddC. Zalcitabine is a pyrimidine nucleoside analogue structurally related to the naturally occurring nucleoside deoxycytidine.
Zalcitabine has the molecular formula C9H13N3O3, molecular weight 211.22 g/mol, and CAS Registry Number 7481-89-2. PubChem identifies it as a pyrimidine 2',3'-dideoxyribonucleoside with antiviral and HIV-1 reverse transcriptase inhibitor activity.
Zalcitabine is chemically described as 2',3'-dideoxycytidine. Its structure consists of a cytosine nucleobase linked to a 2',3'-dideoxyribose sugar moiety. The absence of the 3'-hydroxyl group is particularly important to its pharmacological mechanism because incorporation of its active triphosphate metabolite into viral DNA prevents further DNA chain elongation.
The API is a defined small-molecule nucleoside analogue rather than a peptide, protein or biological product. Zalcitabine is also identified by development and research names including ddC, DDC, Ro-24-2027, and 2',3'-Dideoxy-D-cytidine.
Zalcitabine belongs to the nucleoside reverse transcriptase inhibitor (NRTI) class. After entering cells, zalcitabine undergoes sequential phosphorylation to form its active metabolite, dideoxycytidine 5'-triphosphate (ddCTP).
The active metabolite inhibits HIV reverse transcriptase by competing with the natural substrate deoxycytidine 5'-triphosphate. Once incorporated into viral DNA, the lack of a 3'-hydroxyl group prevents formation of the next phosphodiester bond, resulting in termination of viral DNA chain elongation. This mechanism is documented in the historical FDA HIVID prescribing information.
Zalcitabine therefore represents an important compound in the historical development of nucleoside analogue antiretroviral therapy.
Zalcitabine was developed as an antiretroviral medicine for HIV infection and was historically marketed under the brand name HIVID. IUPHAR/BPS identifies zalcitabine as an approved NRTI antiretroviral drug used in the treatment of HIV/AIDS in combination with other antiretroviral agents.
The compound is now primarily relevant from an API, pharmaceutical research, analytical-reference and historical drug-development perspective because zalcitabine has been discontinued as a routine marketed HIV treatment in many markets.
For pharmaceutical research and API documentation, its classification as a nucleoside analogue and reverse transcriptase inhibitor remains important.
Zalcitabine is described as a white to off-white crystalline powder. The IARC chemical and physical data report a melting point of approximately 215–217°C.
The molecular formula of zalcitabine is C9H13N3O3, with a molecular weight of 211.22 g/mol. The compound has a defined stereochemical configuration corresponding to 2',3'-dideoxycytidine.
Its physicochemical profile makes it distinguishable from related NRTIs such as zidovudine, lamivudine and stavudine.
Zalcitabine has relatively high aqueous solubility compared with many small-molecule pharmaceutical APIs. Historical pharmaceutical data report an aqueous solubility of approximately 76.4 mg/mL at 25°C. The same reference reports solubility in DMSO of approximately 90–100 mg/mL, while ethanol and methanol show substantially lower solubility.
The FDA HIVID package insert also reported an aqueous solubility of 76.4 mg/mL at 25°C, supporting this value as a useful reference for the API's physicochemical profile.
Solubility values should always be interpreted together with temperature, solvent composition and analytical methodology.
Zalcitabine is a stereochemically defined nucleoside analogue. Historical reference data report a specific optical rotation of approximately [α]D25 +81°, measured at a concentration of 0.635 in water.
Because optical rotation is dependent on concentration, temperature, solvent and measurement conditions, this value should be treated as a reference characteristic rather than automatically used as a universal commercial release limit.
Zalcitabine API can be characterized using multiple analytical techniques. Historical USP-related information cited by IARC describes infrared absorption spectrophotometry, liquid chromatography and thin-layer chromatography for identification, with liquid chromatography used for purity and assay determination.
Modern HPLC methods are also available for quantitative determination of zalcitabine in drug substance, pharmaceutical formulations and biological samples. A validated reverse-phase HPLC method has been reported for assay of zalcitabine using UV detection at 265 nm.
For pharmaceutical API quality control, identity, assay, related substances, residual solvents, water content and elemental impurities should be controlled according to the applicable product specification and regulatory requirements.
Zalcitabine API is relevant to pharmaceutical research, analytical reference applications and specialized API development involving nucleoside analogue compounds. An API manufacturing and supply program should provide suitable documentation for identity, purity, assay and impurity control.
The material should be appropriately characterized to confirm its chemical identity and stereochemical integrity. Batch-specific analytical documentation such as a Certificate of Analysis can be used to demonstrate conformity with the agreed specification.
Zalcitabine should be stored according to the validated conditions established for the specific API and packaging system. Appropriate protection from excessive moisture, heat and unsuitable environmental exposure should be maintained.
Pharmaceutical-grade material should be handled under suitable GMP-controlled conditions with appropriate packaging to preserve chemical quality throughout storage and transportation.
Zalcitabine is a synthetic nucleoside analogue and NRTI API historically used in antiretroviral therapy. It is also known as 2',3'-Dideoxycytidine and ddC. The API has the molecular formula C9H13N3O3, molecular weight 211.22 g/mol, and CAS number 7481-89-2.
Its reported physical characteristics include a white to off-white crystalline appearance, melting point of approximately 215–217°C, and aqueous solubility of 76.4 mg/mL at 25°C.
For pharmaceutical API applications, appropriate analytical control of identity, assay, related substances, water content, residual solvents and elemental impurities is important for maintaining consistent quality.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.2% |
| Heavy Metals | NMT 20 ppm |
| pH (1% Solution) | 6.0 – 8.0 |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |
| Specific Rotation | +75° to +87° |
| Melting Point | 215 – 217°C |
| Solubility | Freely soluble in water; approximately 76.4 mg/mL at 25°C |