Min In Phosphate Buffer Research Articles

Synthesis of novel triazine-quinoline-appended naphthalimide sensors for Hg(II) recognition and their structure-activity relationship

Constructing intelligent molecules for specific recognition of metal ions is critically important in environmental and biological fields. In this work, three novel triazine-quinoline-appended naphthalimide fluorescent sensors (NAK1, NAK2, NAK3) with different lengths of the linker were constructed. Research concerning the structure-fluorescence relationships of the three compounds showed that they exhibited distinct photophysical properties in either solution state or solid state. Compound NAK2, containing triazine-quinoline group with an ethylene (-CH2CH2-) linker, showed the strongest liquid state fluorescence emission, and it also displayed superior recognitive selectivity and sensitivity to Hg2+. NAK2 could detect Hg2+ within 2 min in phosphate buffer (PBS)/EtOH (v/v, 3/2) with low detection limit (0.045 μmol/L), being applied in Hg2+ detection in environmental water samples. Job's plot, 1H NMR and DFT calculations demonstrate that NAK2 combined with Hg2+ in 1:1 because of the special coordination holes, causing the change of planarity and electron transfer. This new type of molecular switch provides a new way of building high-performance fluorescence sensors.

Preparation of Gentamicin Sulfate Nanoparticles using Eudragit RS-100 and Evaluation of Their Physicochemical Properties

Improving permeability and absorption of drugs are critical research challenges in pharmaceutical science. Gentamicin sulfate is an aminoglycoside antibiotic, which is very active against gram-negative bacteria; however, it has very poor bioavailability. This study aimed to prepare gentamicin nanoparticles with the intention of increased bioavailability. Accordingly, Eudragit RS-100 nanoparticles loaded with gentamicin sulfate were prepared by the double emulsification and solvent evaporation method, a proper technique for encapsulating hydrophilic molecules. Nanoparticles’ suspensions with polymer to drug ratios of 1:1 ([Formula: see text] and 2:1 ([Formula: see text]) were prepared, lyophilized and evaluated for their production yield, physicochemical properties and morphology. The mean particle size was 195.67[Formula: see text]nm and 228[Formula: see text]nm for [Formula: see text] and [Formula: see text], respectively. The formulations’ loading efficiencies were relatively high (85.73 for [Formula: see text] and 85.20 for [Formula: see text]). The nanoparticles’ surface charge (+40.5[Formula: see text]mV) was sufficient to inhibit their aggregation and facilitate the nanoparticles’ absorption through the gastrointestinal tract. The results of differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR) revealed that drug and polymer stabilized each other by physical interactions between their functional groups. Both formulations presented an initial burst drug release of nearly 20% after 30[Formula: see text]min in phosphate buffer (pH = 7.4). After 24[Formula: see text]h, [Formula: see text] did not release the drug completely, while [Formula: see text] released the whole drug. Overall, nanoparticles with proper characteristics were obtained. This study puts forward the necessity of conducting further research in order to explore the intestinal absorption of these nanoparticles and the possibility of being utilized for oral administration of gentamicin sulfate.

Evaluation of Acacia- Guar Gum Combination as Delayed Release Coating Former on Solid Placebo Tablets

Objectives The present study addresses evaluation of acacia-guar gum combination as an enteric former for tablet coating aiming to add knowledge on how develop the ability of enteric forming ability of acacia-guar combination. Methods Five formulations of enteric coating solution incorporating guar gum as delayed release polymers along with film coating material acacia gum followed by CMC and glycerin as plasticizer and coloring agents were prepared to coat placebo tablet cores. Different enteric coating formulations organized in different acacia : guar gum ratios as 1:1, 1:2, 1:3, 1:4 and 1:6 were sprayed on placebo tablets surface resulted different delayed coated tablets (F1,F2,F3,F4 &F5) respectively. General appearance and physical parameters were evaluated of each. Enteric coated tablets that revealed promising properties were subjected to accelerated stability study for 3 months to explore the influences of physical aging on tablet coat properties. Results Physical parameters of enteric coated tablets post coating within the range of pharmacopeia specification. The disintegration test was carried out in pH 1.2 and pH 6.8 at 37ºC. F1, F2 and F3 enteric tablets disintegrated immediately with no acid resistance compared F4 and F5 enteric tablets showed good acid resistance coat with smooth tablet surfaces and no coat defects. F5 formula contain acacia: guar gum as 1:6 ratio showed delayed release for 30min in pH 1.2 and 15min in phosphate buffer. The study statistically analyzed and concluded that, an efficient and stable acacia-guar enteric coat is achievable with no effect on tablets physical parameters. Guar gum at 60% as a delayed tablet coating material capable of protecting the tablets core from being released in acidic media and be release in the alkaline buffer as well as stable coat under accelerated storage for three months.

Pharmacokinetic incompatibility of the Huanglian-Gancao herb pair

BackgroundPharmacokinetic interaction is one of the most important indices for the evaluation of the compatibility of herbal medicines. Both Gancao (Glycyrrhizae Radix et Rhizoma) and Huanglian (Coptidis Rhizoma) are commonly used traditional Chinese medicines (TCMs). In this study, the influence of Gancao on the pharmacokinetics of Huanglian was systematically studied by using berberine as a pharmacokinetic marker.MethodsExtracts of the herbal pieces of Huanglian and the herb pair (Huanglian plus Gancao) were prepared with boiling water. The concentration of berberine in the samples was analyzed using liquid chromatography-mass spectrometry. The total amounts of berberine in all extract samples were compared. Comparative pharmacokinetic studies of Huanglian and the herb pair were conducted in ICR mice. In vitro berberine absorption and efflux were studied using mice gut sacs. The equilibrium solubility of berberine in the extracts was determined. The in vitro dissolution of berberine was comparatively studied using a rotating basket method.ResultsGancao significantly reduced berberine exposure in the portal circulation (425.8 ng·h/mL vs. 270.4 ng·h/mL) and the liver (29,500.8 ng·h/mL vs. 15,422.4 ng·h/mL) of the mice. In addition, Gancao decreased the peak concentration (Cmax) of berberine in the portal circulation (104.3 ng·h/mL vs. 76.5 ng·h/mL) and liver (4926.1 ng·h/mL vs. 2642.8 ng·h/mL) of mice. Significant influences of Gancao on the amount of berberine extracted (32% reduction), the solubility of berberine (34.7% compared with the control group), and dissolution (88.7% vs. 66.1% at 15 min in acid buffer and 68% vs. 51.8% at 15 min in phosphate buffer) were also revealed. Comparative pharmacokinetic studies in ICR mice indicated that the formation of sediment was unfavorable in terms of berberine absorption (345.3 ng·h/mL vs. 119.8 ng·h/mL).ConclusionsGancao was able to reduce intestinal absorption and in vivo exposure of berberine in Huanglian via the formation of sediment, which caused reductions in the extracted amount, solubility, and dissolution of berberine.

Solubility enhancement of glimperide: Development of solid dispersion by solvent melt method, characterization and dosage form development

The aim of the present work was to develop immediate release dosage form of the solid dispersion of glimperide (GLIM) for potential enhancement in the bioavailability. The solid dispersions of GLIM were prepared with PEG6000, PVP K30 and Poloxamer 188, in 1:1, 1:3 and 1:5 %w/w ratio by using solvent wetting and solvent melt method. The in vitro dissolution parameters (%DE10min, %DE30min, %DE60min, T50% and DP30) were used to select the optimized solid dispersion that was characterized by IR, PXRD, DSC and SEM. The optimized solid dispersion of GLIM (GSDSM3) was used as drug component for immediate release (IR) tablets that were evaluated for physical and pharmacopoeial parameters. The in vitro drug release studies identified G4 as the optimized tablet with a cumulative drug release (CDR) of 99.34% in 30 min in phosphate buffer, pH 7.4. The CDR was higher than the marketed tablet (91.15%, Amaryl®, Sanofiaventis), However, the f1 and f2 were 10.6 and 52 respectively, which confirmed similarity of the dissolution profile(s). Accelerated stability studies confirmed stability up to 6 months at 40°C/75% condition in the HDPE bottle pack.

Co-Amorphization of Ibuprofen by Paracetamol for Improved Processability, Solubility, and In vitro Dissolution

Co-amorphous (COAM) systems of ibuprofen (IB) and paracetamol (PA), in clinical dose ratios, were prepared by ball milling to enhance solubility and dissolution of IB. Subsequently, COAM were characterized by solubility, processability, XRPD, DSC, ATR-FTIR, SEM, in-vitro dissolution and accelerated stability studies. Maximum increase in aqueous solubility of IB was seen in 500:200 mg dose ratio (COAM 1) with 6.7 fold rise from 78.3 ± 1.1 to 522.6 ± 1.29 ∆g/ml. COAM 1 exhibited 99.80 ± 0.58% dissolution of IB at 20 min in phosphate buffer, significantly high (P < 0.05) compared to plain IB. Thus saturation solubility and dissolution rate of IB was found significantly improved unlike PA. The flowability/ processability of COAM system was remarkably improved compared to pure IB, speculated due to as formation of miniscular forms of PA-IB, having strong adhesive interactions. XRPD and DSC results confirmed amorphization of IB. ATR-FTIR results evidenced hydrogen bonding interactions between both the drugs. In accelerated stability studies, flowability, XRPD, DSC and in-vitro dissolution studies demonstrated insignificant changes, thus confirming successful stabilisation of IB by PA.

Developing a stable aqueous enteric coating formulation with hydroxypropyl methylcellulose acetate succinate (HPMCAS-MF) and colloidal silicon dioxide as anti-tacking agent

The purpose of this study was to use statistical design of experiments to develop a stable aqueous enteric coating formulation containing stabilizing excipients, such as polyethylene glycol that can minimize hydroxypropyl methylcellulose acetate succinate aggregation and minimize spray-nozzle clogging at elevated processing temperatures. The mechanisms of stabilization (i.e. charge stabilization and molecular interactions) were studied by performing zeta potential and FTIR studies. Electrostatic stabilization by sodium lauryl sulfate and hydrogen bonding by polyethylene glycol provided dispersion stability and yielded a stable aqueous coating formulation that prevented spray-nozzle clogging. An enteric coated tablet with better gastric resistance was obtained by incorporating fumed silica (Aerosil® R972) as the anti-tacking agent instead of talc. Dissolution testing on the riboflavin enteric coated tablets showed a good enteric release profile without releasing riboflavin in 0.1 N HCl, and completely disintegrating within 10 min in phosphate buffer (pH 6.8).

Comparative study on stabilizing ability of food protein, non-ionic surfactant and anionic surfactant on BCS type II drug carvedilol loaded nanosuspension: Physicochemical and pharmacokinetic investigation

Carvedilol (CAR) in its pure state has low aqueous solubility and extremely poor bioavailability which largely limit its clinical application. The aim of the study is to improve the dissolution rate and the bioavailability of CAR via preparing nanosuspensions with different stabilizers. Antisolvent precipitation-ultrasonication technique was used here. Attempts have been made to use food protein- Whey protein isolate (WPI) as a stabilizer in CAR loaded nanosuspension and also to compare its stabilizing potential with conventional nanosuspension stabilizers such as non-ionic linear copolymer-poloxamer 188 (PLX188) and anionic surfactant-sodium dodecyl sulfate (SDS). Optimized nanosuspensions showed narrow size distribution with particle size ranging from 275 to 640nm. Amorphous state of CAR nanocrystals which also improved the solubility by 16-, 25-, 55-fold accordingly was confirmed by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). From scanning electron microscopy (SEM), flaky shape of PLX188 and SDS nanosuspensions could be revealed but WPI nanosuspension was sphere-shaped. Up to 70% dissolution of loaded drug was observed within 15min in phosphate buffer (pH6.8). A pharmacokinetic study in rats indicated that both Cmax and AUC0–36 values of nanosuspensions were estimated to be 2-fold higher than those of reference, suggesting a significant increase in CAR bioavailability.

Evonik introduces easy-to-disperse fumed silica

The purpose of this study was to use statistical design of experiments to develop a stable aqueous enteric coating formulation containing stabilizing excipients, such as polyethylene glycol that can minimize hydroxypropyl methylcellulose acetate succinate aggregation and minimize spray-nozzle clogging at elevated processing temperatures. The mechanisms of stabilization (i.e. charge stabilization and molecular interactions) were studied by performing zeta potential and FTIR studies. Electrostatic stabilization by sodium lauryl sulfate and hydrogen bonding by polyethylene glycol provided dispersion stability and yielded a stable aqueous coating formulation that prevented spray-nozzle clogging. An enteric coated tablet with better gastric resistance was obtained by incorporating fumed silica (Aerosil® R972) as the anti-tacking agent instead of talc. Dissolution testing on the riboflavin enteric coated tablets showed a good enteric release profile without releasing riboflavin in 0.1 N HCl, and completely disintegrating within 10 min in phosphate buffer (pH 6.8).

Dry formulations of the biocontrol agent Candida sakeCPA‐1 using fluidised bed drying to control the main postharvest diseases on fruits

The biocontrol agent Candida sake CPA-1 is effective against several diseases. Consequently, the optimisation of a dry formulation of C. sake to improve its shelf life and manipulability is essential for increasing its potential with respect to future commercial applications. The present study aimed to optimise the conditions for making a dry formulation of C. sake using a fluidised bed drying system and then to determine the shelf life of the optimised formulation and its efficacy against Penicillium expansum on apples. The optimal conditions for the drying process were found to be 40 °C for 45 min and the use of potato starch as the carrier significantly enhanced the viability. However, none of the protective compounds tested increased the viability of the dried cells. A temperature of 25 °C for 10 min in phosphate buffer was considered as the optimum condition to recover the dried formulations. The dried formulations should be stored at 4 °C and air-packaged; moreover, shelf life assays indicated good results after 12 months of storage. The formulated products maintained their biocontrol efficacy. A fluidised bed drying system is a suitable process for dehydrating C. sake cells; moreover, the C. sake formulation is easy to pack, store and transport, and is a cost-effective process. © 2017 Society of Chemical Industry.

A Method of Low-Temperature Storing of Agarose Slides with Lysed Cells

A method has been developed for a long-term low-temperature storage (-10 to -15°C) of the agarose slides with nucleoids (lysed eukaryotic cells). After lysis of agarose-immobilized cells, the slides were incubated for 30 min in phosphate buffer with 50% glycerol and 100 mM EDTA, thereupon they were stored in a freezer at -10 to -15°C. After long-term storage, the slides were re-incubated for 30 min in lysing solution. The measurements of the baseline and in vitro induced DNA damage in nucleoids of the human and mouse leukocytes, which had been stored in agarose slides at low temperature, showed that DNA damage level determined after a 40-day storage did not significantly differ from that of the fresh slides. The advanced storage method is simple and reliable; it opens the way to avoid cryopreservation of the biological samples and to process little by little a great number of the identically prepared slides.

Complex Formation of Etodolac with Hydrotalcite in Methanol

Abstract Etodolac (2-[(1RS)-1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl]acetic acid) is a nonsteroidal anti-inflammatory drug (NSAID) with a bitter taste. It is slightly soluble in water. Hydrotalcite is a carbonate-type MgAl-layered double hydroxide (CO3-LDH) that is used as an antacid. A complex of etodolac with hydrotalcite was synthesized in methanol via an ion-exchange reaction. The carboxy groups of etodolac were exchanged with carbonate ions in the interlayer region of CO3-LDH. Ion exchange was confirmed by IR and 13C CP/MAS NMR spectra. The complex of nitrate-type LDH (NO3-LDH) was obtained in a mixed solvent composed of equal volumes of methanol or ethanol, and water. The complex had an interlayer distance of 2.20 nm, and a bilayer structure of etodolac in the interlayer region of the complex was observed. The uptake amount increased to 3.0 mmol per gram of CO3-LDH depending on the concentration of etodolac, reaction temperature, and reaction time. The etodolac in the interlayer region of the complex was completely released after 120 min in phosphate buffer. The release of etodolac occurred through exchange with phosphate ions. Thus, the bitterness of etodolac can be suppressed by coating it with LDH.

Electrochemical scission of C–S bond in ethanethiol on a modified β-PbO2 anode in aqueous solution

Specifically odor pollution has attracted more attention over the past several years. Ethanethiol (C2H5SH) is the typical representative due to its lower threshold value. The electrochemical oxidation behavior of ethanethiol solution on a modified β-PbO2 anode with fluoride has been investigated by means of linear sweep voltammetry (LSV). The typical voltammograms of LSV demonstrated that ethanethiol could be oxidized on this electrode at very positive potentials. Results of bulk electrolysis showed that ethanethiol could be thoroughly destructed and eliminated within 35min in phosphate buffer (pH 6.0) under 60mA/cm2 of current density due to the successive attack of hydroxyl radicals (OH) electrogenerated on the surface of β-PbO2 anode. Acetic acid (CH3COOH) was the main intermediate and could be further mineralized, while sulfur atom in ethanethiol was finally converted to nonodorous sulfate ions (SO42-), implying that high deodorization performance could be achieved. According to the sulfur balance, it could be concluded that the scission of ethanethiol was occurred via starting with hydroxyl radical attack and followed by C–S bond cleavage. This study highlights a promising technology for the clean and safe removal of odorous compounds from industrial effluents and will be beneficial for nuisance reduction.

A mediated polyphenol oxidase biosensor immobilized by electropolymerization of 1,2-diamino benzene

A biosensor based on a partially purified polyphenol oxidase (PPO) enzyme was developed by using electropolymerization of [(2,2′-bipyridine)(chloro)(p-cymene)rutenium(II)]chloride] mediator complex and 1,2-diamino benzene (DAB) on a screen printing Pt electrode (1 mm diameter). The electropolymerization was carried out at +0.7 V for 45 min in phosphate buffer (50 mM, pH 7.0) which contained 14.0 U/10 mL polyphenole oxidase, 200 mM DAB and 2.5 mM Ru-mediator complex solutions. Measurement is based on the detection of the oxidation current of the Ru-mediator complex that related to the enzymatic reaction catalyzed by PPO at +0.65 V. The phosphate buffer (50 mM, pH 7.0 containing 0.1 M KCl) and 30 °C were established as being the optimum working conditions. Under the optimum experimental conditions a linear calibration curve was obtained between 5 and 100 μM catechol concentration. The detection limit of the biosensor is 2.385 μM. In the characterization studies of the biosensor some parameters such as effect of Ru-mediator types on the biosensor response, substrate specificity, reproducibility and storage stability were studied. From the experiments, the average value ( x), standard deviation (SD) and coefficient of variation (CV%) were found to be 48.75 μM, ± 1.56 μM, and 3.2% respectively for 50 μM catechol standard.

Synthesis of novel N-diazeniumdiolates based on hyperbranched polyethers

Novel N-diazeniumdiolate based on hyperbranched polyethers(HP-g-DACA/N(2)O(2)) were prepared through a two-step synthesized route. The alkyltrimethoxysilane containing secondary amine groups (DACA) was used to modify the hydroxyl end groups of hyperbranched polyethers (HP) to obtain the precursor hyperbranched diamine (HP-g-DACA). Then HP-g-DACA was reacted with NO at 80psi pressure to be converted into N-diazeniumdiolates. The structures were confirmed using (13)C NMR and IR spectra. UV-vis spectroscopy measurement indicated that the aqueous solution of obtained HP-g-DACA/N(2)O(2) had a characteristic absorption at 246nm. The final HP-g-DACA/N(2)O(2) product showed NO releasing within the prolonged periods of time, and the apparent half-life t(1/2) was more than 11min in phosphate buffer at 37 degrees C. The total amount of NO released from HP-g-DACA/N(2)O(2) could achieve to 0.43micromol/mg and was proportional to the modified degree of HP by DACA. In addition, the NO loading efficiency can be modulated by the modification degree of hyperbranched macromolecular end groups.

Novel sustained release microspheres for pulmonary drug delivery

A novel process for generating sustained release (SR) particles for pulmonary drug delivery is described. High purity nanoparticles of a hydrophilic, ionised drug are entrapped within hydrophobic microspheres using a spray-drying approach. Sustained release of the model drug, terbutaline sulphate (TS), from the microspheres was found to be proportional to drug loading and phospholipid content. Microspheres with a 33% drug loading exhibited sustained release of 32.7% over 180 min in phosphate buffer. Release was not significantly different in simulated lung fluids. No significant burst release was observed which suggested that nanoparticles were coated effectively during spray-drying. The absence of nanoparticles at the microsphere surface was confirmed with confocal microscopy. The sustained release microspheres were formulated as a carrier-free dry powder for inhalation, and exhibited a favourable Fine Particle Fraction (FPF) of 46.5±1.8% and Mass Median Aerodynamic Diameter (MMAD) of 3.93±0.12 μm.

Microbial Safety in Radio‐frequency Processing of Packaged Foods

ABSTRACT: Thermal resistance of Clostridium sporogenes (PA 3679) was determined at 115.6 °C, 118.3 °C, and 121.1 °C (240 °F, 245 °F, and 250 °F, respectively) in phosphate buffer (pH 7.0) and mashed potatoes (pH 6.3) using aluminum thermal‐death‐time (TDT) tubes developed at Washington State Univ. D‐values were 1.8, 1.1, and 0.62 min in phosphate buffer and 2.2, 1.1, and 0.61 min in mashed potatoes at 115.6 °C, 118.3 °C, and 121.1 °C, respectively. Z‐values were 12 °C and 10 °C in phosphate buffer and mashed potatoes, respectively. The thermal inactivation kinetic results were then used to validate a novel thermal process based on 27.12 MHz radio frequency (RF) energy. Trays of mashed potatoes inoculated with PA 3679 were subjected to 3 processing levels: target process (F0∼4.3), under‐target process (F0∼2.4), and over‐target process (F0∼7.3). The microbial challenge test data showed that microbial destruction from the RF process agreed with the calculated sterilization values. This study suggests that thermal processes based on RF energy can produce safe and shelf‐stable packaged foods.

In vitro uptake and stability study of pVEC and its all-D analog.

A key step in the development of new hydrophilic pharmaceuticals is to get them through biological barriers. Cell-penetrating peptides, CPPs, have been shown previously to enter cells both in vitro and in vivo by a non-endocytotic mechanism and to be able to carry large cargo molecules with them. Recently, we showed that a small peptide, pVEC, from murine vascular endothelial cadherin, has the characteristics to be classified as a protein derived CPP. Here we have further investigated pVEC together with its all-D analog for cellular uptake, intra- and extracellular stability, and their enzymatic degradation. The two peptides, pVEC and all-D pVEC, translocate into aortic endothelial cells and murine fibroblasts by a non-endocytotic mechanism. In phosphate buffer, pVEC remains intact while the C-terminal lysine is quickly removed in human serum and serum-containing media. Both pVEC and pVEC without the C-terminal Lys were detected by mass spectrometry inside the two cell types tested. The pVEC half-life is 10.5 min in phosphate buffer containing 10 units of trypsin and 44.6 min in phosphate buffer containing 4.2 units of carboxypeptidase A and 18 units of carboxypeptidase B. In contrast topVEC, the all-D analog remains intact in serum and resists enzymatic degradation.

Colocalization and Interaction of Cyclooxygenase-2 with Caveolin-1 in Human Fibroblasts

Results from our previous study suggest that cyclooxygenase-2 (COX-2) induced by phorbol 12-myristate 13-acetate (PMA) may be localized to caveolae-like structures (Liou, J.-Y., Shyue, S.-K., Tsai, M.-J., Chung, C.-L., Chu, K.-Y., and Wu, K. K. (2000) J. Biol. Chem. 275, 15314-15320). In this study, we determined subcellular localization of COX-2 and caveolin-1 by confocal microscopy. COX-2 in human foreskin fibroblasts stimulated by PMA (100 nm) or interleukin-1beta (1 ng/ml) for 6 h was localized to plasma membrane in addition to endoplasmic reticulum and nuclear envelope. Caveolin-1 was localized to plasma membrane, and image overlay showed colocalization of COX-2 with caveolin-1. This was confirmed by the presence of COX-2 and caveolin-1 in the detergent-insoluble membrane fraction of cells stimulated by PMA. Immunoprecipitation showed complex formation of COX-2 with caveolin-1 in a time-dependent manner. A larger quantity of COX-2 was complexed with caveolin-1 in PMA-treated than in interleukin-1beta-treated cells. Purified COX-2 complexed with glutathione S-transferase-fused caveolin-1, which was not inhibited by the scaffolding domain peptide. Caveolin-1-bound COX-2 was catalytically active, and its activity was not inhibited by the scaffolding domain peptide. These results suggest that COX-2 induced by PMA and interleukin-1beta is colocalized with caveolin-1 in the segregated caveolae compartment. Because caveolae are rich in signaling molecules, this COX-2 compartment may play an important role in diverse pathophysiological processes.

Chemical model for phosphine-induced lipid peroxidation

Phosphine (PH 3 ) from hydrolysis of metal phosphides is highly toxic and is important for control of stored-product insect pests (AlP, Mg 3 P 2 ) and rodents (Zn 3 P 2 ). This fumigant inhibits respiration and induces lipid peroxidation in insects and mammals. PH 3 (from Mg 3 P 2 ) and H 2 O 2 , acting for 15 min in phosphate buffer (pH 7.4), oxidized cod liver oil (high in unsaturated lipids) to malondialdehyde. Both Mg 3 P 2 and H 2 O 2 were found to be necessary for this lipid peroxidation, which under optimal conditions produced a seven-fold increase in malondialdehyde relative to basal levels in cod liver oil with H 2 O 2 but no PH 3 . Under the same conditions, 15-, 9- and 2-fold increases in malondialdehyde were obtained from ethyl arachidonate, methyl linoleate and methyl oleate. Small amounts of hydroxyl radical from PH 3 /H 2 O 2 were trapped with salicylic acid. Reactive oxygen species for lipid peroxidation may therefore be derived from direct reaction of PH 3 with H 2 O 2 as an alternative hypothesis to their respiration-linked formation.