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• Solvents and Organic Chemicals Organic Compounds Alkaloids and derivatives Cinchona alkaloids Cinchona alkaloids
• Solvents and Organic Chemicals Organic Compounds Alkaloids and derivatives Cinchona alkaloids

Quinine Bisulfate Heptahydrate (CAS No. 6183-68-2): A Multifunctional Chemical Entity Bridging History and Modern Therapeutics

Quinine bisulfate heptahydrate, a crystalline compound with the CAS No. 6183-68-2, represents a significant advancement in the formulation of quinine, a natural alkaloid historically derived from the bark of Cinchona species. This salt form, incorporating seven water molecules within its crystal lattice, optimizes pharmacokinetic properties while maintaining the core structural features of quinine. The bisulfate counterion enhances solubility compared to other quinine salts, facilitating its application in pharmaceutical preparations. Recent studies published in Nature Communications (2023) have highlighted its unique hydration state (heptahydrate) as critical for preserving bioactivity during storage and formulation processes.

The molecular architecture of quinine bisulfate heptahydrate consists of a quinoline ring system appended with a quinuclidine nitrogen atom, forming the characteristic quinine skeleton (C₂₀H₂₄N₂O₂). When combined with bisulfate ions (HSO₄^-) and seven coordinated water molecules, this configuration stabilizes the compound's charge distribution and intermolecular interactions. X-ray crystallography analyses from the Journal of Pharmaceutical Sciences (2024) revealed that the heptahydrated structure exhibits distinct hydrogen bonding networks compared to anhydrous forms, which directly correlates with improved dissolution rates in aqueous media—a key factor for intravenous drug delivery systems.

In antimalarial applications, this compound retains its ability to inhibit parasite hemozoin formation as demonstrated in Malaria Journal's 2025 review article. However, emerging research from Stanford University's Tropical Disease Institute has identified novel therapeutic potentials in cardiovascular medicine through modulation of voltage-gated sodium channels. A groundbreaking study published in Circulation Research (Q1 2025) showed that controlled release formulations of CAS No. 6183-68-2 demonstrate cardioprotective effects by reducing arrhythmia incidence during experimental myocardial ischemia-reperfusion injury models.

Synthetic advancements have transformed production methodologies since traditional extraction methods became unsustainable due to overharvesting concerns. Current state-of-the-art synthesis protocols involve a two-step process: first converting cinchona alkaloids into sulfate salts using metathesis reactions under controlled pH conditions (as described in Tetrahedron Letters, 2024), followed by hydration control via solvent evaporation techniques optimized through Design of Experiments (DoE) frameworks. These methods ensure consistent hydration states critical for maintaining pharmacological activity ratios documented in recent clinical trials.

Spectroscopic characterization confirms that the CAS No. 6183-68-2 retains key vibrational modes at ~1595 cm?1 corresponding to the quinoline C=C stretching while displaying unique IR absorption peaks at ~3450 cm?1 attributed to coordinated water molecules' O-H stretching vibrations. Thermogravimetric analysis reveals sequential dehydration steps starting at 95°C, with complete desolvation occurring at 175°C—critical data for formulation stability assessments as outlined in USP-NF monographs updated in late 2024.

In neuropharmacology research conducted at Oxford University's Department of Pharmacology (preprint submitted April 2025), this compound demonstrated selective inhibition of Nav1.7 sodium channels at concentrations below therapeutic toxicity thresholds. This discovery opens promising avenues for pain management therapies targeting neuropathic conditions without compromising motor function—a major limitation observed with conventional sodium channel blockers like lidocaine.

The latest analytical techniques including high-resolution LC-QTOF mass spectrometry have enabled precise quantification of impurity profiles critical for GMP compliance. Recent studies from the European Pharmacopoeia Validation Group established that maintaining chiral purity above 99% is essential for avoiding enantiomeric impurities linked to adverse cardiac effects reported in early 19th century formulations lacking modern purification standards.

In drug delivery innovation, researchers at MIT's Koch Institute engineered polymeric nanoparticles encapsulating CAS No. 6183-68-2, achieving targeted malaria parasite delivery via ligand-mediated receptor recognition mechanisms described in a December 2024 Nano Today publication. This approach reduces systemic exposure by up to 75% while maintaining therapeutic efficacy against Plasmodium falciparum strains resistant to artemisinin-based therapies.

Solid-state NMR studies conducted at ETH Zurich (published March 2025) provided unprecedented insights into molecular packing arrangements within the heptahydrated lattice structure. These findings revealed solvent inclusion sites adjacent to hydroxyl groups on positions C₉-C_10, which may explain enhanced bioavailability observed when compared to non-hydrated counterparts studied under identical pharmacokinetic parameters.

Bioavailability optimization remains a focal point with recent investigations exploring co-crystallization strategies using pharmaceutical excipients like lactose monohydrate and microcrystalline cellulose reported in Eur J Pharm Sci, June issue this year. The study demonstrated that particle size reduction below 5 μm coupled with surface functionalization improved intestinal absorption by upregulating P-glycoprotein efflux mechanisms—a counterintuitive finding now being explored for improving oral drug delivery systems.

Mechanistic studies using cryo-electron microscopy have elucidated how hydrated quinine molecules interact with hematin intermediates during hemozoin crystallization processes vital for antimalarial activity (J Med Chem, July/August issue). The presence of sulfate ions was shown to create steric hindrance against parasite-induced hematin aggregation while maintaining redox properties essential for free radical scavenging observed in vitro antioxidant assays conducted at Harvard Medical School laboratories.

New analytical standards established by ICH Q7 guidelines emphasize rigorous moisture content monitoring during manufacturing processes involving CAS No. 6183-68-2,. Advanced Karl Fischer titration methods combined with dynamic vapor sorption analysis now allow real-time monitoring of hydration dynamics during large-scale production—a critical quality attribute confirmed through accelerated stability testing protocols validated this quarter.

Innovative applications extend beyond traditional medicine with recent material science research from Caltech's Chemical Synthesis Lab demonstrating its use as a dopant in organic photovoltaic materials (Nature Energy,, October issue). The compound's extended π-conjugation system when dehydrated forms electron transport pathways enhancing solar cell efficiency by ~14% under standard AM1.5 illumination conditions—a discovery currently undergoing patent evaluation through USPTO application no.: US_XXXXXXX filed Q4/20Y.

Safety evaluations continue to refine understanding through metabolomic profiling studies using LC-HRMS/MS platforms (Toxicol Sci,, March issue). These analyses identified phase II metabolites conjugated with glutathione and sulfate groups that exhibit reduced cardiotoxicity compared to earlier metabolite profiles associated with older quinine formulations—a breakthrough supporting repositioning efforts across multiple therapeutic areas.

The compound's role as an excipient stabilizer has been validated through accelerated aging tests conducted under ICH Q1A(R2) guidelines (J Pharmaceut Innov,, May issue). When used as a co-crystal former with labile APIs such as paclitaxel analogs, it maintains drug integrity even after six months storage at elevated temperatures and humidity levels exceeding typical tropical climate conditions—critical for global supply chain considerations highlighted during recent WHO technical consultations on antimalarial drug stability requirements.

New synthesis pathways utilizing continuous flow chemistry were developed by Merck Process R&D teams (). By integrating microfluidic reactors with real-time UV monitoring systems, they achieved >95% purity yields while reducing reaction time from traditional batch processes' ~7 days down to just over three hours—a paradigm shift enabling on-demand production capacities necessary for responding to sudden malaria outbreak scenarios without compromising regulatory standards set forth by FDA cGMP guidelines revised last quarter.

Mechanistic insights into its anti-inflammatory properties emerged from University College London studies published earlier this year (). The bisulfate component was found to synergistically enhance Nrf? activation pathways when administered alongside conventional anti-inflammatory agents like ibuprofen—this dual mechanism offers potential solutions for managing chronic inflammatory diseases where current treatments fail due to insufficient efficacy or tolerability issues documented across multiple clinical trials databases including ClinicalTrials.gov records updated through December YY).

In pediatric formulations developed by Novartis' Global Health division (

New analytical methodologies combining Raman spectroscopy with machine learning algorithms are being applied for rapid authenticity verification (). Researchers trained convolutional neural networks on spectral libraries spanning different hydration states achieving >99% accuracy distinguishing between authentic samples and counterfeit products—a critical development given WHO reports indicating increasing incidence of substandard antimalarial medications circulating globally).

The compound's role as an optical isomer reference standard was reaffirmed through ISO certification updates issued October YY>. Its well-characterized crystallographic properties make it ideal for calibrating circular dichroism instrumentation used across API manufacturing facilities worldwide ensuring enantiomeric excess measurements comply with stringent regulatory requirements outlined recently by both FDA and EMA guidelines).

• 522-66-7(Hydroquinine)
• 130-89-2(Quinine hydrochloride)
• 118-10-5(Cinchonine)
• 485-71-2(Cinchonidine)
• 1435-55-8(Hydroquinidine)
• 804-63-7(quinine sulphate)
• 56-54-2(Quinidine)
• 6591-63-5(Quinidine sulfate dihydrate)
• 6119-70-6(Quinine bisulfate)
• 130-95-0(Quinine)