Loratadine Impurity J

Details:

Loratadine Impurity J

Product Information

• Product Code：L019010

• English Name：Loratadine Impurity J

• English Alias：4,8-dichloro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11(6H)-one

• CAS No.：133330-60-6

• Molecular Formula：C??H?Cl?NO

• Molecular Weight：278.13

Advantages

• High-Purity Reference Standard：Confirmed by HPLC (≥99.0%), NMR (1H, 13C), HRMS, and elemental analysis, suitable for Loratadine impurity analysis and quality control.

• Stability Assurance：Stable for 36 months at -20℃ under light-protected, sealed storage; degradation rate <0.3% in methanol-acetonitrile mixture within 6 months.

Applications

• Quality Control Testing：Used for UPLC-MS/MS detection of Impurity J in Loratadine API and formulations, controlling content to meet ICH Q3A standards (single impurity limit ≤0.1%).

• Process Optimization Research：Monitors impurity formation during Loratadine synthesis, reducing generation by >30% by adjusting chlorination temperature (e.g., 50-60℃) and reaction time.

• Method Validation：Serves as a standard for developing impurity detection methods, verifying UPLC resolution (≥3.0) and LOD (0.01 ng/mL).

Background Description

Loratadine, a highly effective and long-acting tricyclic antihistamine, is used to relieve various allergic symptoms by blocking H1 receptors. Impurity J, a process-related impurity in its synthesis, may originate from chlorination side reactions of the benzocycloheptapyridine ring. Its chlorine atoms and ketone group may affect drug lipophilicity, metabolic stability, and safety. Strict impurity control for antihistamines is critical to drug quality, making research on this impurity essential.

Research Status

• Detection Technology：UPLC-MS/MS with C18 column (1.7μm) and 0.1% formic acid-acetonitrile gradient elution achieves separation within 7 minutes, with LOD of 0.005 ng/mL for trace impurity analysis.

• Formation Mechanism：Formed by electrophilic substitution of benzocycloheptapyridinone with chlorinating agents (e.g., phosphorus oxychloride); optimizing chlorinating agent dosage and reaction pH inhibits side reactions.

• Safety Evaluation：In vitro cytotoxicity shows IC?? of 195.6 μM against Hela cells (Loratadine IC??=12.3 μM), with lower toxicity than the main drug but requiring strict content control. Long-term stability testing is ongoing to monitor degradation under high temperature and humidity conditions.

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