A Liquid Chromatography-mass Spectrometry Method to Determine the Content of Genotoxic Impurity Piperidine in Rimonabant.

Objective: To establish and determine the content of the genotoxic impurity piperidine in the active pharmaceutical ingredient (API) of rimonabant using a liquid chromatography-mass spectrometry (LC-MS) method. This study underscores the importance of detecting piperidine due to its potential health risks, including carcinogenic and mutagenic effects, thus highlighting the critical need for rigorous quality control in pharmaceutical products. Methods: An Atlantis C18 column (5 µm, 3.9×100 mm) was chosen for separation due to its high efficiency and selectivity for piperidine, with a gradient elution of 0.05% formic acid-water (A) and methanol (B) as the mobile phase at a flow rate of 1.0 mL/min. The column temperature was optimized at 30°C to ensure peak resolution and sensitivity, the injection volume was set to 5.0 µL to minimize sample consumption while maintaining detectability, and the analysis time was kept at 7 min for efficient throughput. Results: Piperidine demonstrated excellent linearity in the concentration range of 0.03-0.40 µg/mL (R>0.99), with a detection limit of 0.01010 µg/mL. This detection limit is significantly lower than regulatory thresholds, indicating the method's high sensitivity compared to existing methods and its adequacy for regulatory compliance in pharmaceutical quality control. Conclusion: This LC-MS method not only demonstrated high accuracy, good repeatability, and strong durability but also sets a benchmark for future research, regulatory practices, and pharmaceutical quality control. By accurately detecting low levels of genotoxic impurities like piperidine, this method supports the development of safer drug formulations and underscores the importance of stringent quality control measures in the pharmaceutical industry.

New diterpenoids from the rhizomes of Hedychium forrestii.

A novel hexanorditerpenoid, hedychin C (1), and a new diterpenoid, hedychin D (2), were isolated from the rhizomes of Hedychium forrestii. Their structures and absolute configurations were unambiguously established by means of extensive spectroscopic data (IR, UV, HRMS, and NMR) and electronic circular dichroism (ECD) calculations. This is the first report of naturally occurring labdane-type hexanorditerpenoid. Compound 1 was proved to have moderate cytotoxicity against XWLC-05 cell line with an IC50 value of 53.6 µM.

Hedychins A and B, 6,7-Dinorlabdane Diterpenoids with a Peroxide Bridge from Hedychium forrestii.

Hedychins A (1) and B (2), two unprecedented 6,7-dinorlabdane ditepenoids with a peroxide bridge, were obtained from the rhizomes of Hedychium forrestii. Their structures and absolute configurations were unequivocally established by a combination of spectroscopic data and X-ray single-crystal diffractions. Their plausible biosynthetic pathway was proposed. Compound 2 exhibited cytotoxicity against HepG2 and XWLC-05 cell lines with IC50 values of 8.0 and 19.7 µM, respectively.