Low concentrations of soybean lecithin nanoparticles had a positive impact on Holstein bulls' cryopreserved semen.

Spermatozoa can experience negative changes when subjected to freezing and thawing, including lowered motility, viability and acrosome response. Herein, the effects of different concentrations of soybean lecithin nanoparticles on cryopreserved Holstein bull semen were examined. Semen was collected, cryopreserved and utilized for sperm kinetic parameter analysis following dilution, equilibration and thawing with 0.5% soybean lecithin (E1), the control extender, and 0.75% (E2), 0.5% (E3), 0.25% (E4) and 0.125% (E5) of lecithin nanoparticles. Results revealed that following dilution, the progressive motility (PM) at E3, E4 and E5 of lecithin nanoparticles was higher (p < .05) than it was for E2. After equilibration, compared to the E1, E2, and E3 values, the PM, vitality, normal morphology, membrane integrity and intact acrosome values at the E5 were consistently greater (p < .05). Comparing the percentages of intact acrosome and membrane integrity at E2 and E3 to E4 and E5, a substantial decrease (p < .05) was seen. Following thawing, the percentage of PM improved at E2 and E5, even though their mean PM values were similar (p > .05) compared to E1, E3 and E4. Vigour and progression parameters of sperm (DAP, DCL, DSL, VAP, VCL, VSL and STR) at E5 were higher (p < .05) than those at E1, E2, E3 and E4. In conclusion, the cryopreserved sperm from Holstein bulls revealed outstanding properties both after equilibration and after thawing with 0.125% lecithin nanoparticles, and they were sensitive to high dosages.

An eco-friendly HPLC-UV method for the determination of risedronate in its bulk and tablet dosage form with application to content uniformity, dissolution and stability testing.

Risedronate is a nitrogen-containing bisphosphonate for the treatment and prevention of postmenopausal osteoporosis. The current work aims to develop a novel green HPLC-UV method for the rapid analysis of risedronate sodium in bulk and tablet formulation. The analyzed samples were separated on Waters Atlantis dC18 (150 mm × 3.9 mm; 5 µm) column using a green mobile phase consisting of potassium phosphate buffer pH 2.9 and potassium edetate buffer pH 9.5 in a ratio of 1:2, the final pH was adjusted to 6.8 with phosphoric acid, the mobile phase was pumped at a rate of 1.0 mL/min, with column temperature set at 30 °C, eluted samples were detected at 263 nm and the chromatographic run time was 3.0 min. The method was found to be linear over the concentration range of 14-140 µg/mL with a correlation coefficient (r2) of 0.9994. Accuracy and precision were evaluated from three QC samples (LQC, MQC and HQC) together with the five calibrators where the percentage accuracy was found to be 101.84%. Processed quality control samples of risedronate sodium were tested for stability at different conditions, short term, long term and freeze- thaw stability. The current method was further extended to study the content uniformity of Actonel® tablets following United States Pharmacopoeia (USP) guidelines. The proposed method was fully validated as per ICH guidelines.

Electrophilic Aromatic Synthesis of Radioiodinated Aripiprazole: Experimental and DFT Investigations.

BACKGROUND: Aripiprazole is a quinolinone derivative. It shows a high affinity for neurotransmitters dopamine and serotonin receptors, which can overcome the blood-brain barrier (BBB) to reach the central nervous system (CNS) to exert therapeutic effects. Its radioiodination may lead to high radiochemical yield and improved its affinity. Aripiprazole radioiodination is an aromatic electrophilic substitution. OBJECTIVE: Herein, we investigate the favorable atom site of the aromatic electrophilic substitution of aripiprazole by calculating the Fukui indices of heavy atoms and ESP charges of the parent molecule. METHODS: The calculations have been carried out at the B3LYP/LanL2DZ level of theory. The iodinated aripiprazole structure is confirmed by comparing the experimental and the predicted 1H NMR chemical shifts of the parent molecule and its iodinated forms. RESULTS: Finally, the electronic properties of aripiprazole and its iodinated form were calculated at the same level of theory. Nucleophilic Fukui indices and ESP charges calculations confirm that C8 is the most favorable site of the electrophilic substitution. The calculated electronic properties (e.g, gap energy, electron affinity, and electronegativity) of aripiprazole and its iodinated form reveal the higher reactivity of iodinated aripiprazole compared with aripiprazole. CONCLUSION: This may explain the higher affinity of iodinated aripiprazole and the increase of its radiochemical yield.

Radioiodination and biodistribution of newly synthesized 3-benzyl-2-([3-methoxybenzyl]thio)benzo[g]quinazolin-4-(3H)-one in tumor bearing mice.

3-Benzyl-2-((3-methoxybenzyl)thio)benzo[g]quinazolin-4(3H)-one was previously synthesized and proved by physicochemical analyses (HRMS, 1H and 13C NMR). The target compound was examined for its radioactivity and the results showed that benzo[g]quinazoline was successfully labeled with radioactive iodine using NBS via an electrophilic substitution reaction. The reaction parameters that affected the labeling yield such as concentration, pH and time were studied to optimize the labeling conditions. The radiochemical yield was 91.2 ±â€¯1.22% and the in vitro studies showed that the target compound was stable for up to 24 h. The thyroid was among the other organs in which the uptake of 125I-benzoquinazoline has increased significantly over the time up to 4.1%. The tumor uptake was 6.95%. Radiochemical and metabolic stability of the benzoquinazoline in vivo/in vitro and biodistribution studies provide some insights about the requirements for developing more potent radiopharmaceutical for targeting the tumor cells.

Selective and sensitive spectrofluorimetric quantification of velpatasvir in presence of sofosbuvir. Application to their co-formulated tablet.

A new sensitive, rapid and simple spectrofluorimetric method was utilized for the assessment of velpatasvir (VPS) in its bulk form as well as in its combined tablet with sofosbovir (SFV). The technique relies on measuring the native fluorescence of VPS in methanol at 385 nm and 400 nm after excitation at 295 nm. The fluorescence-concentration plots were rectilinear through the range of 2.0-20.0 ng mL-1 at both emission maxima with lower detection limits of 0.146 ng mL-1 and 0.378 ng mL-1, and lower quantification limits of 0.444 ng mL-1 and 1.147 ng mL-1 at 385 nm and 400 nm, respectively. The proposed method was appropriately used for the analysis of VPS in its commercial tablet formulation and the results were in good agreement with those achieved with the applied comparison method.

Preparation of cyclotron-produced 186Re and comparison with reactor-produced 186Re and generator-produced 188Re for the labeling of bombesin.

The radioisotopes (186)Re and (188)Re have been extensively investigated for various forms of radiotherapy due to their useful and high-abundance beta particle emissions, low-abundance and imageable gamma-rays, and chemical resemblance to technetium. In addition, (188)Re is available in no-carrier-added (NCA) form from long lived W-188 generators, whereas (186)Re can be produced in large quantities from reactors, although not in NCA form. However, NCA (186)Re can be produced on a cyclotron by a (p,n) reaction on (186)W. The purpose of this study was to compare labeling of the peptide bombesin with these three forms of rhenium radioisotopes. Cyclotron-produced NCA (186)Re was separated radiochemically from enriched (186)W (96.9%) targets using high-purity methyl ethyl ketone (MEK). The resulting (186)Re-MEK was then loaded onto a small alumina column to separate the resulting NCA (186)Re from any remaining (186)W. The experimental levels of impurities associated with (186)Re at the end of the separation process were found to be 5.7 x 10(-6) Ci of (182)Re (0.57%, t(1/2) = 12.7 h) and 1.283 x 10(-5) Ci of (182m)Re (1.28%, t(1/2) = 2.67 days). The radionuclidic purity of the separated (186)Re was found to be 99.6%, whereas the chemical identity was determined by reversed phase high-performance liquid chromatography (RP-HPLC) to be perrhenate ((186)ReO(4)(-)). Generator-produced (188)ReO(4)(-) from a (188)W/(188)Re generator (Oak Ridge National Laboratory) and CA (186)ReO(4)(-) produced from a (185)Re(n,gamma)(186)Re reaction at the University of Missouri Research Reactor (MURR) were used for comparison with the NCA (186)Re in subsequent studies. N(3)S-5-Ava-BBN(7-14)NH(2) conjugates provide flexibility for designing (186,188)Re-labeled conjugates that retain high in vitro and in vivo specificity targeting of GRP receptor-expressing cells. This study showed that the N(3)S-5-Ava-BBN(7-14)NH(2) could be labeled with (186,188)Re following the preconjugation, postmetallation approach. The (186,188)Re(V)O-N(3)S-5-Ava-BBN(7-14)NH(2) complexes were found to form stable complexes following the reduction of perrhenate (Re(VII)O(4)(-)) with stannous chloride at room temperature, as verified by HPLC and stability studies. The radiolabeling yield was found to be >90%. The HPLC chromatograms of (186,188)Re-N(3)S-5-Ava-BBN(7-14)NH(2) complexes revealed two peaks for each conjugate, reflecting the presence of syn- and anti-isomers, which were resolvable by HPLC but re-isomerized on separation. The biodistribution studies showed that the compounds were excreted through the renal and hepatobiliary systems and demonstrated receptor-specific uptake with an average pancreas accumulation of 8.15% ID/g at 1 h postinjection. Administration of cold BBN effectively blocked pancreatic uptake and further reflects the high specificity this conjugate has for the GRP receptors. At low levels of radioactivity, radiolysis effects were not observed. Scale-up may or may not elicit this effect, particularly for the higher energy beta emitter (188)Re. The biodistribution studies demonstrated that the CA and NCA (186,188)Re conjugates behaved similarly, raising the question of whether NCA (186,188)Re is necessary for specific tumor receptor targeting.