Adulteration of the Herbal Weight Loss Products by the Illegal Addition of Synthetic Antiobesity Medications: A Pilot Study.

BACKGROUND: Some anorexic agents are used to fraudulent augmentation herbal weight loss formulations. This study was designed to evaluate the potential existence of illicit substances in 63 herbal weight loss formulations collected from local apothecaries in Hamadan, Iran. METHODS: The thin-layer chromatography method was applied for the primary screening of potential illicit substances in the samples. The positive samples were analyzed using an isocratic high-performance liquid chromatography method. RESULTS: The results showed that 26.98% of the samples contained 17.76 ± 6.02 mg/cap of sibutramine. Daily therapeutic dose intake of sibutramine is in the range of 5 to 15 mg daily. CONCLUSION: Since apothecaries have advised consumers to take at least two capsules a day, it seems that the blood concentration of sibutramine will likely rise beyond the therapeutic concentration and become toxic. Therefore, the usage of such products could pose serious risks to consumers' health.

Quantification of 4-Methylimidazol in NMRI Mice Plasma and Cerebrospinal Fluid (CSF) by Using Liquid Chromatography Tandem Mass Spectrometry.

A sensitive method using ion-pair extraction was developed by liquid chromatography tandem mass spectrometry (LC-MS/MS) for measurement of 4-methylimidazole (4-MI) in NMRI mice plasma and cerebrospinal fluid (CSF). Detection was done by electrospray positive ionization mass spectrometry in the multiple-reaction monitoring (MRM) mode. The validation method was applied to quantification of 4-MI in plasma and CSF samples using oral doses of 100, 200, and 300 mg/kg in NMRI mice. The efficiency of the method was evaluated in terms of linearity (R 2> 0.99), recovery (98-107%, 3 levels) and precision (8-10%, 3 levels, n = 6). Limit of detection (LOD) and limit of quantification (LOQ) were 25 ng/mL and 50 ng/mL, respectively. The results obtained showed that the exposure to oral doses of 4-MI in mice makes different concentrations in plasma and CSF and causes significant changes in mice. This study was the first report for determination of 4-MI in plasma and CSF samples in mice. Our results suggest that LC-MS/MS-based on ion-pair extraction is a robust method with high detection ability for measurement of 4-MI in plasma and CSF samples. Therefore, the developed method can be useful for evaluation and monitoring of imidazole derivatives in biological samples.

Crystal-liquid Fugacity Ratio as a Surrogate Parameter for Intestinal Permeability.

BACKGROUND: We assessed the feasibility of using crystal-liquid fugacity ratio (CLFR) as an alternative parameter for intestinal permeability in the biopharmaceutical classification (BCS) of passively absorbed drugs. METHODS: Dose number, fraction of dose absorbed, intestinal permeability, and intrinsic dissolution rate were used as the input parameters. CLFR was determined using thermodynamic parameters i.e., melting point, molar fusion enthalpy, and entropy of drug molecules obtained using differential scanning calorimetry. RESULTS: The CLFR values were in the range of 0.06-41.76 mole percent. There was a close relationship between CLFR and in vivo intestinal permeability (r > 0.8). CLFR values of greater than 2 mole percent corresponded to complete intestinal absorption. Applying CLFR versus dose number or intrinsic dissolution rate, more than 92% of tested drugs were correctly classified with respect to the reported classification system on the basis of human intestinal permeability and solubility. CONCLUSION: This investigation revealed that the CLFR might be an appropriate parameter for quantitative biopharmaceutical classification. This could be attributed to the fact that CLFR could be a measure of solubility of compounds in lipid bilayer which was found in this study to be directly proportional to the intestinal permeability of compounds. This classification enables researchers to define characteristics for intestinal absorption of all four BCS drug classes using suitable cutoff points for both intrinsic dissolution rate and crystal-liquid fugacity ratio. Therefore, it may be used as a surrogate for permeability studies. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

The effect of different concentrations of chlorhexidine gluconate on the compressive strength of mineral trioxide aggregate.

Background and aims. Substituting chlorhexidine (CHX) for water has been shown to enhance antimicrobial activity of mineral trioxide aggregate (MTA). The purpose of this study was to compare the compressive strength of MTA mixed with distilled water, 0.12% and 0.2% chlorhexidine. Materials and methods. MTA was mixed according to manufacturer's instructions in group I (n = 20). In groups II & III, 0.12% and 0.2% CHX liquid was substituted for water, respectively. Samples were condensed with moderate force into 20 tubes with 1.5×5 mm dimensions and were allowed to set for 72 hours at 37°C in 100% humidity. After being removed from the molds, their compressive strength was determined using Instron testing machine. Each group was divided into two subgroups according to the time of testing (at 72 hours, and one week). Fractured surfaces of 4 specimens in each group were then evaluated under Scanning Electron Microscope (SEM) to determine their microstructure. One-way ANOVA, Tukey, and paired sample t-test was used for statistical analysis. P < 0.05 was set as significant. Results. There was no significant difference between three groups in terms of their compressive strength after 72 hours. However, the compressive strength of group II was significantly higher than group I (P = 0.034) and group III (P = 0.021) after one week. Crystalline microstructure was similar in all groups. Conclusion. Substitution of 0.012% chlorhexidine for water significantly increased the compressive strength of MTA at 1 week without significant change in crystalline structure.