Quinine sulfate dihydrate
[CAS# 207671-44-1]

Identification

• Classification: API >> Antiparasitic drug
• Name: Quinine sulfate dihydrate
• Synonyms: (R)-[(2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol;sulfuric acid;dihydrate
• Molecular Formula: C₄₀H₅₄N₄O₁₀S
• Molecular Weight: 782.94
• CAS Registry Number: 207671-44-1
• EC Number: 690-615-6
• SMILES: COC1=CC2=C(C=CN=C2C=C1)[C@H]([C@@H]3C[C@@H]4CCN3C[C@@H]4C=C)O.COC1=CC2=C(C=CN=C2C=C1)[C@H]([C@@H]3C[C@@H]4CCN3C[C@@H]4C=C)O.O.O.OS(=O)(=O)O

Properties

• Melting point: 233 - 235 ºC (Decomposes) (Expl.)

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319

Discovory and Applicatios

Quinine sulfate dihydrate is a crystalline salt form of quinine, an alkaloid originally isolated from the bark of cinchona trees native to South America. The therapeutic value of quinine was recognized by indigenous populations well before its introduction into European medicine in the 17th century, where it became the first effective treatment for malaria. Quinine itself is a stereochemically complex molecule belonging to the quinoline alkaloid family and contains multiple chiral centers, a quinoline moiety, and a quinuclidine ring system. When prepared as quinine sulfate dihydrate, the compound exhibits improved stability and solubility properties, making it a suitable dosage form for oral administration in the treatment of malaria.

The sulfate salt is typically obtained by neutralizing quinine base with sulfuric acid in aqueous medium, producing the crystalline sulfate, which incorporates two molecules of water per quinine sulfate unit. The dihydrate form is the most common pharmaceutical grade, and its crystalline structure has been characterized using X-ray diffraction techniques. Historically, quinine sulfate was supplied in tablet or capsule form and widely used to manage Plasmodium falciparum infections before the advent of synthetic antimalarial drugs. Although it has largely been replaced by newer agents such as chloroquine, mefloquine, and artemisinin derivatives due to efficacy and tolerability considerations, quinine sulfate dihydrate remains relevant in clinical settings, particularly for resistant malaria strains.

In addition to its antimalarial use, quinine sulfate has a documented history of application in the management of nocturnal leg cramps, although its use for this indication has diminished due to safety concerns. Reports of serious adverse effects, including thrombocytopenia, cardiac arrhythmias, and hypersensitivity reactions, led regulatory agencies such as the U.S. Food and Drug Administration to restrict its use primarily to malaria. Nevertheless, quinine-containing beverages such as tonic water, which contain much lower concentrations of quinine, continue to be consumed recreationally, reflecting the compound’s distinctive bitter taste.

The discovery of quinine and its subsequent isolation in the early 19th century by French chemists Pierre Joseph Pelletier and Joseph Bienaimé Caventou marked a milestone in natural product chemistry and pharmacology. It was the first plant-derived compound to be systematically purified and used in modern medicine, setting the stage for the development of alkaloid chemistry as a discipline. The isolation of quinine not only revolutionized the treatment of malaria but also influenced colonial expansion into tropical regions by providing a prophylactic measure against the disease.

Applications of quinine sulfate dihydrate today remain primarily medical. Its role is restricted to specific malaria treatments, especially where resistant strains are present. It is still listed on the World Health Organization’s Model List of Essential Medicines, underlining its enduring importance in global health despite the availability of newer antimalarial drugs. Advances in pharmaceutical chemistry have improved formulations, but the basic sulfate dihydrate salt remains the most reliable form for therapeutic use. Its history reflects both the evolution of natural product research and the interplay between medicine, pharmacognosy, and public health.

References

Pelletier P J and Caventou J B (1820) Recherches chimiques sur les quinquinas. Annales de Chimie et de Physique 15 289–318 URL

Achan J, Talisuna A O, Erhart A, Yeka A, Tibenderana J K, Baliraine F N, Rosenthal P J, and D'Alessandro U (2011) Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria. Malaria Journal 10 144 DOI: 10.1186/1475-2875-10-144

World Health Organization (2023) World Health Organization model list of essential medicines, 23rd list. WHO Technical Report URL