Physical and Chemical Properties
- Molecular Formula: C₂₂H₂₄N₂O₈
- Molecular Weight: 444.44 g/mol
- Appearance: Yellow crystalline powder (hyclate form is more water-soluble)
- Solubility:
- Sparingly soluble in water (∼50 mg/mL at pH 2, improves in acidic conditions).
- Freely soluble in DMSO (∼100 mg/mL), methanol, and dilute acids/bases.
- Melting Point: 201–203°C (decomposes upon heating).
- pKa Values: 3.5 (phenolic -OH), 7.7 (dimethylammonium), 9.5 (enolic -OH).
- Spectroscopy:
- UV-Vis λ_max: 269 nm (pH 2), shifts to 350 nm (pH 7–9) due to tautomerization.
- Characteristic IR peaks: 1610 cm⁻¹ (C=O stretch), 1520 cm⁻¹ (N-H bend).
- Stability:
- Degrades under UV light (requires amber vials).
- Unstable in strong bases (epimerization) or oxidizing agents.
Mechanism of Action and Pharmacology
- Primary Action: Binds to the 30S ribosomal subunit, blocking tRNA docking → inhibits bacterial protein synthesis.
- Spectrum of Activity:
- Gram-positive: Streptococcus pneumoniae, Staphylococcus aureus (MRSA if susceptible).
- Gram-negative: E. coli, Haemophilus influenzae.
- Atypical pathogens: Chlamydia, Rickettsia, Plasmodium (malaria), Wolbachia (symbiont in filariasis).
- Pharmacokinetics:
- Absorption: 90–100% oral bioavailability (unaffected by food).
- Distribution: Wide tissue penetration (including CSF, bones, prostate).
- Metabolism: Minimal hepatic metabolism; excreted unchanged in urine/feces.
- Half-life: 18–22 hours (permits once-daily dosing).
