A green approach for metoclopramide quantification in pharmaceutical products: new HPLC and spectrophotometric methods.

Green spectrophotometric and HPLC methods have been developed for the quantification of metoclopramide. In the spectrophotometric method, it was determined by direct absorbance measurement at 273 nm wavelength using ultrapure water as solvent. The Extend C18 column was used for the HPLC method. The mobile phase system consisted of a combination of ethanol and formic acid solution (pH 2.0; 30:70 v/v). Isocratic elution was applied and the flow rate was set at 1.0 mL min-1. Metoclopramide was detected at 273 nm. The methods performed were economical, rapid, environmentally friendly, and simple, providing metoclopramide analysis within 5 min. The methods have been successfully applied in pharmaceutical products without matrix interference. The results of the application of the developed methods to pharmaceutical products were statistically compared and no significant difference was observed between the methods. In addition, the greenness assessment of the developed methods was performed using AGREE software. Our developed methods, based on the use of solvents such as ethanol and water, are proposed as a more environmentally and analyst-friendly option for the quantification of metoclopramide in pharmaceutical products than other methods currently in use.

Radiolabeling of morphine with (131)i and its biodistribution in rats.

This study was conducted to determine the possible radiopharmaceutical potential of morphin labeled with (131)I. Morphine was extracted from dry capsules of the opium poppy (Papaver somniferum L.), purified by high-performance liquid chromatography, and characterized with nuclear magnetic resonance and infrared spectroscopy. The purified compound was labeled with (131)I. Male Albino Wistar rats (18) were used for receptor blockage and unblockage biodistribution studies. Tissue distribution studies showed that radiolabeled morphine had higher uptake in lung, liver, small intestines, large intestines, and stomach than the other tissues. The highest uptake of radiolabeled compounds in rats' brain was found to be in the midbrain and hypothalamus. After receptor blockage with morphine, uptake of (131)I-morphine decreased in the lungs, liver, kidney, testis, prostate, spinal cord, cerebellum, hippocampus, striatum, and temporal cortex with respect to receptor unblockage studies of rats. This study concludes that the labeling yield of (131)I-morphine was high, high amount of (131)I-morphine was found in the hypothalamus, and (131)I-morphine has enough stability for diagnostic scanning.

Synthesis of a novel antiestrogen radioligand (99mTc-TOR-DTPA).

This study was aimed at developing a hydrophilic radioligand as an antiestrogen drug derivative to be used for imaging breast tumors. Toremifene [TOR; 4-chloro-1,2-diphenyl-1-(4-(2-(N,N-di-methylamino)ethoxy)phenyl)-1-butene, as citrate salt] was selected as the starting material to be derived, since it has been used extensively as an antiestrogen drug for treatment and prevention of human breast cancer. An antiestrogen drug derivative, TOR attached to diethylenetriamine pentaacetic acid (DTPA), was synthesized by two experimental treatments, including a purification and a reaction step. We described the synthesis of this TOR derivative, (3Z)-4-{4-[2-(dimethylamino) ethoxy] phenyl}-3,4-diphenylbut-3-en-1-ylN,N-bis[2-(2,6-dioxomorpholin-4-yl)ethyl]glycinate (TOR-DTPA), in detail. Mass spectroscopy confirmed the expected structures. TOR-DTPA was labeled with technetium-99m ((99m)Tc), using stannous chloride (SnCl(2)) as the reducing agent. Biodistribution studies were performed on female Albino Wistar rats. Quality controls, radiochemical yield, and stability studies were done utilizing high-performance liquid chromatography, radioelectrophoresis, thin-layer chromatography, and thin-layer radiochromatography methods. The synthesized compound was found to be hydrophilic and anionic, with high stability for the duration of the testing period in vitro. The results indicated that the radiolabeled compound has estrogen-receptor specificity, especially for the breast tissue. It is highly possible that this compound could be used for imaging breast tumors as a novel technetium-labeled hydrophilic estrogen derivative radioligand.

Synthesis and biodistribution studies of two novel radiolabeled estrone derivatives.

BACKGROUND: Two 99mTc-DTPA attached estrone derivatives were synthesized and their radiopharmaceutical potential was determined using female albino Wistar rats. MATERIALS AND METHODS: Two novel radiolabeled estrone derivatives, 99mTc-2,2',2"2"'-(2,2'-(2-(3-methoxy-13-methyl-17-oxo-7, 8, 9, 11, 12, 13, 14, 15, 16, 7-decahydro-6H- cyclopenta[a]phenanthren-2-ylamino)-2- oxoethylazanediyl) bis(ethane-2,1-diyl)) bis(azanetriyl) tetraacetic acid (99mTc-2-DTPA-3-methoxy estrone) and 9mTc-2,2',2",2'"-(2,2'- (2-(3-methoxy-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro- 6H-cyclopenta[a]phenanthren-4-ylamino)-2-oxoethylazanediyl) bis(ethane-2,1-diyl))bis(azanetriyl)tetraacetic acid (99mTc-4-DTPA-3-methoxy estrone) were synthesized starting from estrone (3-hydroxy-13-methyl-7,8, 9,11,12,13,15,16-octahydro-6H-cyclopenta[a]phenanthren-17(14H)-one) and DTPA anhydride (2-(bis(2-(2,6-dioxomorpholino)ethyl)amino)acetic acid) as potential estrogen receptor imaging agents. The products were crystallized in ethyl alcohol (95%), purified by high performance liquid chromatography (HPLC) and characterized by nuclear magnetic resonance (NMR) and infrared spectroscopy (IR). The effect of the radiolabeled compounds on the biological behaviour of the molecules was evaluated through biodistribution studies in female albino Wistar rats. The rats were sacrificed at various time intervals, their organs were removed, and the activities of organs were counted using a gamma counter equipped with a Cd(Te) solid state detector. RESULTS AND CONCLUSION: Organ uptake was calculated as activity/gram tissue and time versus activity curves were generated. The tissue distribution studies exhibited a receptor-mediated uptake in the target organs of the rats for each compound. Both 99mTc-2-DTPA-3-methoxy estrone and 99mTc-4-DTPA-3-methoxy estrone were stable in vitro and were mainly excreted through the hepatobiliary pathway. The biological data showed that the 99mTc-2-DTPA-3-methoxy estrone had higher uptake in the target tissues than the 99mTc-4-DTPA-3-methoxy estrone. The favourable in vitro/in vivo stability and biodistribution profiles suggest that these radioligands are good candidates for further exploration of their potential clinical applications.

Effect of X-radiation on lipid peroxidation and antioxidant systems in rats treated with saponin-containing compounds.

The aim of this study was to investigate the effect of three saponin-containing plant species extracts (Aesculuc hippocastanum L. seed extract [AHE], Medicago sativa L. extract [MSE] and Spinacia oleracea L. extract [SOE]) on lipid peroxidation and on antioxidant systems in rats exposed to X-rays (XR). The rats were divided into three categories. The first category served as controls and received only a standard diet. The second category served as the radiation group and received 5 and 10 Gy XR dose. The third category (XR+extract-treated) received plant extracts (25.0 or 50.0 mg kg(-1) live weight) and 5 or 10 Gy XR dose. Blood samples were analyzed for their content of malondialdehyde (MDA), reduced glutathione (GSH), plasma vitamin C, beta-carotene and retinol. In animals receiving XR, the plasma MDA (P < 0.001) value significantly increased but the level of GSH (P < 0.01), vitamin C (P < 0.001), retinol and beta-carotene (P < 0.001) decreased significantly with increasing XR doses. In the XR+extract-treated groups, the concentrations of MDA increased significantly with increasing radiation but their concentrations decreased significantly with increasing extract concentrations. Plasma concentrations of GSH, beta-carotene, retinol and vitamin C in XR+extract-treated groups decreased significantly with increasing XR dose but their concentrations increased with increasing extract doses. Further, comparison of blood samples of XR+extract-treated groups with those from the control group showed that GSH, beta-carotene, retinol and vitamin C values increased significantly but that MDA values decreased significantly. The results showed that all extracts have enhanced the antioxidant status and decreased the incidence of free radical-induced lipid peroxidation in blood samples of rats exposed to XR. However, the antioxidant effect of AHE-administered animals was more effective than that of MSE- and SOE-administered whole-body XR rats. We conclude that the supplementation with saponin-containing extracts may serve to reinforce the antioxidant systems, thus having protective effect against cell damage by XR.

Effect of grape seed extract on lipid peroxidation, antioxidant activity and peripheral blood lymphocytes in rats exposed to x-radiation.

The present studies were designed to evaluate supplemental grape seed extract (GSE) and vitamin E supplements on lipid peroxidation, on antioxidant systems and peripheral blood lymphocytes in rats exposed to x-rays. Three groups of rats were investigated: a control group (CG) received intraperitoneal (i.p.) physiological serum 1 mL/day (n=10), i.p.; a vitamin E group (VG) received 50 mg/kg/day (n=10); an i.p. grape seed extract group received 50 mg/kg/day (n=10). Four weeks later, a 6 Gy radiation dose was given to the rats. Blood samples were taken 24 h later after irradiation and lymphocyte, malondialdehyde (MDA), reduced glutathione (GSH), nitrate, nitrite, reduced ascorbic acid, retinol, beta-carotene and ceruloplasmin concentrations were analysed. The levels of GSH (p<0.05), retinol (p<0.001), beta-carotene (p<0.05) and ceruloplasmin concentration (p<0.001) in the GSE group were found to be higher than in the control group but the level of MDA (p<0.001) and nitrite concentration (p<0.05) in rats supplemented with GSE were found to be lower than in the control group. The results indicate that GSE enhanced the antioxidant status and decreased the incidence of free radical-induced lipid peroxidation in blood samples of rats exposed to x-radiation. The antioxidant effect of GSE given to animals was more effective than vitamin E administered before whole-body irradiation in rats.

In vivo radioprotective effects of Nigella sativa L oil and reduced glutathione against irradiation-induced oxidative injury and number of peripheral blood lymphocytes in rats.

Radiotherapy is one of the most common therapies for treating human cancers. Several studies have indicated that irradiation induces reactive oxygen species (ROS), which play an important role in radiation damage of the cell. It has been shown that Nigella sativa L. (NS) and reduced glutathione (GSH) have both an antiperoxidative effect on different tissues and a scavenger effect on ROS. The purpose of this study was to determine the antioxidant and radio-protective roles of NS and GSH against irradiation-induced oxidative injury in an experimental model. The NS group was administrated NS (1 mL/kg body weight), the GSH group was injected GSH (150 mg/kg body weight) and the control group was given physiologic saline solution (1 mL/kg body weight) for 30 consecutive days before exposure to a single dose of 6 Gy of radiation. Animals were sacrificed after irradiation. Malondialdehyde, nitrate, nitrite (oxidative stress markers) and ascorbic acid, retinol, beta-carotene, GSH and ceruloplasmin (nonenzymatic antioxidant markers) levels and peripheral blood lymphocytes were measured in all groups. There were statistically significant differences between the groups for all parameters (P < 0.05). Whole-body irradiation caused a significant increase in blood malondialdehyde, nitrate and nitrite levels. The blood oxidative stress marker levels in irradiated rats that were pretreated with NS and GSH were significantly decreased; however, non-enzymatic antioxidant levels were significantly increased. Also, our results suggest that NS and GSH administration prior to irradiation prevent the number of alpha-naphthyl acetate esterase peripheral blood T lymphocytes from declining. These results clearly show that NS and GSH treatment significantly antagonize the effects of radiation. Therefore, NS and GSH may be a beneficial agent in protection against ionizing radiation-related tissue injury.

A correlative study between 99mTc-ESTCPTA and 99mTc-MIBI in rats.

Tissue distribution of the 99mTc labeled derivative of the estrogen compound 3,17-alpha-estradiolyl propyl 1,4,8,11-tetraazacyclotetradecanyl-l-(4-methylbenzoic acid) ester (ESTCPTA), which has an 3,17-alpha-estradiolyl propinol coupled to l-(4-methylbenzoic acid)1,4,8,11-tetraazacyclotetradecane (CPTA), was compared to 99mTc-MIBI (methoxyisobutyl isonitrile) in female Albino Wistar rats. Tissues of interest included lung, liver, heart, kidneys, spleen, stomach, intestines, pancreas, muscle, blood, breast, ovary, fat, and uterus. 99mTc-ESTCPTA uptake by the uterus and ovary, as ER-rich tissues, was highly selective. Maximum uptakes for 99mTc-MIBI and 99mTc-ESTCPTA are 90 min in breast, ovary and uterus. The pancreas also showed significant receptor saturated and unsaturated ratios for 99mTc-ESTCPTA. Results are sufficiently encouraging to generate further evaluation of these and related compounds as possible estrogen receptor based tumor imaging and therapeutic agents in estrogen-rich tissues.