Ziprasidone Hydrochloride is an active pharmaceutical ingredient belonging to the atypical antipsychotic class. It is the hydrochloride salt of ziprasidone and is used in the development and manufacture of pharmaceutical formulations containing ziprasidone. The commonly used pharmaceutical form is Ziprasidone Hydrochloride Monohydrate, identified by CAS No. 138982-67-9, molecular formula C₂₁H₂₄Cl₂N₄O₂S, and molecular weight approximately 467.4 g/mol.
Ziprasidone itself has the molecular formula C₂₁H₂₁ClN₄OS, while the anhydrous hydrochloride salt is identified by CAS No. 122883-93-6 and has a molecular weight of approximately 449.4 g/mol. Because the anhydrous and monohydrate forms have different molecular weights and water-content requirements, pharmaceutical manufacturers should clearly identify the required form when purchasing or specifying the API.
Ziprasidone Hydrochloride Monohydrate is chemically described as a hydrochloride hydrate of ziprasidone. The compound contains a benzisothiazole-piperazine structural moiety connected through an ethyl chain to a chlorinated indolinone structure. PubChem identifies the monohydrate under CAS No. 138982-67-9 and lists its molecular formula as C₂₁H₂₄Cl₂N₄O₂S.
The anhydrous hydrochloride form is represented by the formula C₂₁H₂₂Cl₂N₄OS and CAS No. 122883-93-6. This distinction is particularly important for API quality control because the monohydrate contains one molecule of water of crystallization and therefore has a different molecular weight from the anhydrous form.
Ziprasidone Hydrochloride is associated with pharmaceutical products used in the atypical antipsychotic category. Regulatory information for the original Geodon product identifies the active pharmaceutical substance in the capsules as ziprasidone hydrochloride monohydrate. The regulatory documentation describes the material as a white to slightly pink powder.
Ziprasidone has pharmacological activity at several neurotransmitter receptors. It has antagonist activity at dopamine D₂ and serotonin 5-HT₂A receptors, among other receptor interactions. The FDA documentation notes that the precise mechanism responsible for clinical efficacy in schizophrenia is not fully established, while its pharmacology includes dopamine and serotonin receptor activity.
Ziprasidone Hydrochloride is described in the United States Pharmacopeia (USP) with specific requirements for identification, assay, organic impurities, water determination and other quality attributes. The USP monograph provides an assay acceptance range of 97.5% to 102.0%, calculated on the appropriate anhydrous and solvent-free basis.
The USP requirements also control specified and unspecified organic impurities. Current USP revision information lists individual acceptance limits including NMT 0.10% for Ziprasidone Related Compound A, NMT 0.15% for chloroindolinone, and NMT 0.20% for several specified related compounds. The total impurities limit is NMT 0.50%.
These pharmacopoeial requirements provide an important framework for analytical quality control when evaluating Ziprasidone Hydrochloride API. Actual commercial release specifications should nevertheless correspond to the applicable pharmacopoeia, regulatory dossier and batch-specific Certificate of Analysis.
The physical form of Ziprasidone Hydrochloride has a direct effect on its water specification. According to the USP monograph, Ziprasidone Hydrochloride Monohydrate has a water content requirement of 3.7%–5.0%, whereas the anhydrous form has a water limit of NMT 2.0%.
This difference is important when purchasing, testing, storing or formulating the API. The monohydrate should not be treated as equivalent to the anhydrous hydrochloride when calculating molecular weight, assay basis or water content.
Analytical identification of Ziprasidone Hydrochloride can be performed using appropriate spectroscopic and chromatographic techniques. Pharmaceutical quality control commonly includes infrared identification and chromatographic testing. The USP monograph includes specific chromatographic procedures for assay and organic impurity determination.
Typical API quality-control programs may evaluate:
The exact testing program should be based on the applicable specification and regulatory requirements for the intended market.
Ziprasidone Hydrochloride Monohydrate is described in regulatory pharmaceutical documentation as a white to slightly pink powder. The material has limited aqueous solubility, and its physical and chemical properties should be considered during formulation development and analytical method development.
Because the API exists in different solid forms, physical characterization can be important for pharmaceutical development. Manufacturers should verify the supplied material against the agreed specification and Certificate of Analysis rather than relying solely on generic physical-property information.
Ziprasidone Hydrochloride API is relevant to pharmaceutical manufacturers developing or manufacturing dosage forms containing ziprasidone. The API can be evaluated for compliance with applicable pharmacopoeial requirements, including assay and impurity specifications.
For formulation and manufacturing operations, control of API identity, purity, water content and solid form is important. In particular, the distinction between Ziprasidone Hydrochloride Monohydrate and anhydrous Ziprasidone Hydrochloride should be maintained throughout procurement, quality control and manufacturing documentation.
Pharmaceutical companies sourcing Ziprasidone Hydrochloride should specify the required chemical form, pharmacopoeial standard, quantity, packaging requirements and analytical documentation. A typical API procurement package may include a Certificate of Analysis (CoA), specification sheet, Safety Data Sheet (SDS) and applicable regulatory documentation.
For the monohydrate form, the relevant chemical identity is CAS 138982-67-9, with molecular formula C₂₁H₂₄Cl₂N₄O₂S and molecular weight approximately 467.4 g/mol. For anhydrous Ziprasidone Hydrochloride, the corresponding identity is CAS 122883-93-6, formula C₂₁H₂₂Cl₂N₄OS, and molecular weight approximately 449.4 g/mol.
Quality documentation is an important part of pharmaceutical API procurement. Buyers should verify that the supplied batch meets the agreed specification and that the analytical documentation corresponds to the actual chemical form being supplied.
Important quality attributes may include HPLC assay, impurity profile, water determination, residue on ignition and identification testing. For pharmacopoeial material, the applicable current monograph should be used as the primary reference for release testing.
Ziprasidone Hydrochloride is a specialized pharmaceutical API requiring appropriate control of chemical identity, solid form, assay, impurities and water content. Pharmaceutical manufacturers and formulation companies can specify their required grade, pharmacopoeial standard, quantity and documentation requirements when evaluating the API.
For Ziprasidone Hydrochloride Monohydrate, the product should be identified using CAS No. 138982-67-9 and molecular weight approximately 467.4 g/mol. The monohydrate's USP water requirement of 3.7%–5.0% should also be distinguished from the anhydrous form's NMT 2.0% requirement.
For bulk API requirements, appropriate quality documentation and batch-specific analytical data should be reviewed before pharmaceutical manufacturing use. This helps ensure that the material supplied corresponds to the specified Ziprasidone Hydrochloride form and applicable pharmacopoeial requirements.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 97.5% – 102.0% |
| Residue on Ignition | NMT 0.2% |
| Individual Impurity | NMT 0.2% |
| Total Impurities | NMT 0.5% |
| Water Content | 3.7% – 5.0% (monohydrate) |