The attenuated total reflection technique in combination with the terahertz technique is being investigated to find rotatable bonds, which are considered to be one of the rules of thumb given by Veber et al. The results were obtained using a pulsed terahertz spectrometer equipped with a Dove prism, in which the ATR technique was applied. Two forms of samples were used to check the methodology: polycrystalline, and saturated solutions in ethyl alcohol. Histidine, as one of the best-studied pharmacological preparations, was used in the experiment to test our research. Four spectral details were found in the terahertz band, including one for which intermolecular vibrations are responsible, and three others for which intramolecular vibrations, such as rotatable bonds, may be responsible. Histidine molecules that are dissolved in alcohol, and thus free of intermolecular bonds, reveal rotations around three bonds. Therefore, the accuracy of the THz-TDS-ATR research methodology is confirmed in the search for intramolecular vibrations of the molecule, including rotatable bonds. The number of the latter is a guide for designing drug-like candidate compounds. The research methodology presented in the article can support pharmacological research and the pharmaceutical industry.

Background and Rationale: Spinal fusion surgery is one of the standard treatments for degenerative and traumatic spine diseases. delayed union or pseudarthrosis of grafting bone after surgery create more serious problems in performing spinal fusion surgery for patients with glucocorticoid-induced osteoporosis (GIOP).
Purpose: To elucidate the effect of intermittent administration of TPTD or alendronate on spinal fusion in rats with GIOP.
Study Design: An experimental animal study of rats under continuous glucocorticoid (GC) exposure undergoing spinal fusion surgery and administration of TPTD or Alindronate.
Methods: 24 Male albino rats weighing 250-300 g. Six rats were subcutaneously injected with saline per week for 6 weeks before. The other 18 rats were subcutaneously injected with MP five times per week at a dose of 5 mg/kg/d for 6 weeks before surgery. After 6 weeks of MP administration, rats were randomized into three groups before surgery; rats in the control group (CNT group; n6) were given subcutaneous injections of 0.9% saline five times per week for 6 weeks, and rats in the alendronate group (n6) were given subcutaneous injections of 15 mcg/kg/d of alendronate for 6 weeks. and rats in the TPTD group (n6) were given subcutaneous injections of 40 mcg/kg/d of TPTD five times per week for 6 weeks. After grouping, all rats were underwent posterolateral spinal fusion (L4–L5) with iliac crest autograft. The following assessments were performed: microstructural analysis of the fusion mass and adjacent vertebrae (L6),; fusion assessment, with manual palpation testing; and bone histomorphometrical analysis of the fusion mass.
Results: In the alendronate group and In the TPTD group, values for bone volume and other bone microstructural parameters at the fusion mass increased and peaked 4 weeks after surgery, and these values were significantly greater than those for the control (CNT) group at 4 and 6 weeks after surgery. Fusion assessment showed that fusion rate was higher in the alendronate group and in the TPTD group than in the CNT group (CNT group: 0%, alendronate group 67%; TPTD group: 84%). Conclusions: Under continuous GC exposure in a rat model of spinal fusion, alendronate or intermittent TPTD administration were stimulating bone formation at the fusion mass and increasing the fusion rate. Intermittent TPTD administration also improved bone microarchitecture of adjacent vertebrae.

Residual solvents are volatile organic substances, derived from synthesis or manufacturing processes, and can be present in active pharmaceutical ingredients (API). Due to their toxic potential, they must be eliminated, or at least have their content controlled according to official specifications. We aimed to optimize and validate an analytical method by gas chromatography with liquid injection to determine the residual solvents dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) in the API ketoconazole. A divinylbenzene column coupled to a flame ionization detector (FID) was used and helium was chosen as the carrier gas. In selectivity there was a good separation of both peaks besides other impurities present in the sample, compared to the reference chemical substances. The method presented linearity, showing correlation coefficients of 0.99984 and 0.99976 and determination coefficients of 0.99951 and 0.999984 for DMF and DMSO, respectively. The residuals evaluation showed homoscedastic distribution and the slope met the requirements for the F test. In precision, the tested solutions revealed a relative standard deviation (RSD) value of 1.88% for DMF and 1.56% for DMSO, below the limit of 10.0%. In verifying accuracy using the recovery test, the results from 101.4 to 106.9% of the established limit, were satisfactory. Finally, robustness was assessed by means of premeditated variations of critical parameters for the method, such as sim-ultaneous changes in the column lot (+1.34% for DMF and −0.16% for DMSO) or gas flow (−1.85% for DMF and −1.52% for DMSO). Thus, the method developed is satisfactory for the purpose for which it’s intended.