teriparatide (Xinfutai Pro)

Development of Long-Acting Teriparatide Analogues through Iterative Peptide Scanning and Site-Specific Modification by Serine/Threonine Ligation.

Liu Biyao B, Song Kaixuan K, Sui Hongli H, Li Zhuang Z et al.

Teriparatide, the only FDA-approved osteoanabolic drug for osteoporosis, suffers from poor metabolic stability and requires frequent subcutaneous injections, leading to suboptimal patient compliance. To find optimized teriparatide derivatives, we herein report an iterative peptide scanning strategy followed by a serine/threonine ligation (STL) chemistry for site-specific modifications. Using our 2-hydroxyphenol-pseudoproline (ψ2-hydroxyphenolpro) modification (HPM) method, two series of teriparatide analogues with different types of substituents were successfully prepared for scanning the modifiable sites and their expansibility. Through chemoselective acylation of embedded serine/threonine residues, several fatty acids of unequal lengths were introduced to further improve the pharmacokinetic properties of scanning derivatives. Among the 12 lipidated analogues, 54, 55, 62, and 63 exhibited potent antiosteoporotic activities in vitro and in vivo close to those of native teriparatide. The most effective compound, 62, also demonstrated significantly enhanced serum stability and may serve as a promising candidate for further development of long-acting antiosteoporotic pharmaceuticals.

Sensitive Quantification of N-Nitroso Dibutylamine Impurities in Tramadol Tablets Using Optimized LC-MS/MS Method.

Reddy G Saiteja GS, Naveen Nimbagal Raghavendra NR, Shankar M M

NDBA, a recognized genotoxic and carcinogenic impurity in pharmaceutical products, is employed as a model compound. As a result, regulatory agencies worldwide have imposed stringent testing requirements for Nitrosamine impurities, and there is a demand for sensitive and selective analytical methods for their detection. The purpose of this study was to develop and validate a Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) method for the accurate determination of NDBA impurities in Tramadol tablets, thereby overcoming the limitations of High Performance Liquid Chromatography (HPLC) in identifying low-level impurities. Selectivity and sensitivity of the LC-MS/MS method were optimized, and the Limit of Quantitation (LOQ) was set to 5% and the Limit of Detection (LOD) to 3% of the specification limit. The linearity was characterised over a range of 5% to 150% relative to the specification limit. At several concentration levels within the analytical range, the precision and accuracy were determined. In the specified range, the developed method was found to be linear (R² > 0.999). Low relative standard deviation precision studies yielded results consistent with those obtained with this analytical method, and accuracy assessments demonstrated that the method could quantitatively measure NDBA over a range of concentrations. The method was suitable for routine quality control and met and exceeded regulatory performance requirements (LOQ and LOD). The developed LC-MS/MS method demonstrated high sensitivity, specificity, and reproducibility for the quantification of NDBA in Tramadol tablets. The method met ICH validation criteria, including acceptable precision (%RSD <5%), strong linearity (r2 = 0.9980), and satisfactory recovery (97.8-115%). The low LOD (0.002 ppm) and LOQ (0.003 ppm) confirm its suitability for detecting trace-level genotoxic impurities, ensuring regulatory compliance and pharmaceutical safety. It was established that a validated LC-MS/MS method provides a reliable, sensitive, and selective approach for determining NDBA impurities in Tramadol tablets. The use of this method enables compliance with the most stringent regulatory standards for pharmaceutical product safety and efficacy.

Correction to "Validated RP-HPLC-UV Method for Simultaneous Quantification of Aminophenazone, Dipyrine, and Antihistamine in Pharmaceutical Formulations Considering Dipyrine Decomposition".

[This corrects the article DOI: 10.1155/ianc/7435313.].

Measuring vapour-liquid equilibria (VLE) using benchtop NMR.

Liyanage Isanthi R IR, Bowen Reuben R, Hartshorn Richard M RM, Holland Daniel J DJ

Vapour-liquid equilibria data are essential in the design of chemical processes. Existing measurement techniques require relatively large quantities of material, making them challenging to apply to new processes for expensive or toxic species. We report a novel method for measuring vapour-liquid equilibrium data of binary liquid mixtures using benchtop 1H NMR spectroscopy close to ambient pressure. Vapour and liquid compositions were directly obtained from NMR measurements, showing good agreement with predictions from state-of-the-art thermodynamic models. Furthermore, following calibration, the benchtop NMR results were used to obtain measurements of vapour pressure. Results were obtained from as little as 0.5 mL of sample, extending the range of systems for which vapour-liquid equilibria can be measured.