Simultaneous spectrophotometric determination of paracetamol, phenylephrine and chlropheniramine in pharmaceuticals using chemometric approaches.

BACKGROUND AND THE PURPOSE OF THE STUDY: The linear multivariate calibration models such as principal components regression (PCR) and partial least squares regressions (PLS1 and PLS2) due to the mathematical simplicity and physical or chemical interpretability are sufficient and generally preferred method for analysis of multicomponent drugs. In this study, simultaneous determination of paracetamol, phenylephrine and chlorpheniramine in pharmaceuticals using chemometric methods and UV spectrophotometry is reported as a simple alternative technique. MATERIAL AND METHODS: Principal components regression (PCR) and partial least squares regressions (PLS1 and PLS2) were used for chemometric analyses of data obtained from the spectra of paracetamol, phenylephrine and chlorpheniramine between wavelengths of 200 to 400 nm at several concentrations within their linear ranges. The analytical performance of these chemometric methods were characterized by relative prediction errors and recoveries (%) and compared with each other. RESULTS: PCR, PLS1 and PLS2 were successfully applied to a tablet formulation, with no interference from excipients as indicated by the recovery. However, the PLS1 shows better results due to its flexibility and mathematical principals. CONCLUSION: The proposed methods are simple and rapid requiring no separation step, and can be easily used as an alternative in the quality control of drugs.

Effect of Ramadan fasting on some indices of insulin resistance and components of the metabolic syndrome in healthy male adults.

The purpose of the present study was to evaluate the effect of Ramadan fasting on insulin sensitivity in subjects with the metabolic syndrome. Males (n 55; age 34.1 (sd 8.9) years) with the metabolic syndrome were studied. Blood pressure, waist circumference, body weight, HDL-cholesterol (HDL-C), TAG, fasting plasma glucose (FPG), fasting blood insulin and insulin resistance indices (quantitative insulin sensitivity check index (QUICKI), homeostasis model assessment of insulin resistance (HOMA-IR) and reciprocal index of HOMA-IR (1/HOMA-IR)) were evaluated before and after 30 d of Ramadan fasting (two meals at 12 h intervals). The dietary intake was estimated by 24 h recall before and after fasting. The total daily energy intake was decreased by 234.6 (sd 88.2) kJ/d in the fasting period (P = 0.005). 1/HOMA-IR, QUICKI and HDL-C were significantly increased (P = 0.005, P = 0.001 and P = 0.004) and FPG significantly decreased (P < 0.005) after fasting. Simple linear regression analysis demonstrated that HOMA-IR, 1/HOMA-IR and QUICKI were related to waist circumference after intervention (r 0.458, P < 0.001; r - 0.396, P < 0.05; r - 0.342, P < 0.05). In conclusion, the present study showed that the combined change in the number and timing of meals and portioning of the entire intake into only two meals per d may increase insulin sensitivity in subjects with the metabolic syndrome even when the decrease in energy consumption is minimal.

Simultaneous spectrophotometric determination of paracetamol, ibuprofen and caffeine in pharmaceuticals by chemometric methods.

In this study, the simultaneous determination of paracetamol, ibuprofen and caffeine in pharmaceuticals by chemometric approaches using UV spectrophotometry has been reported as a simple alternative to using separate models for each component. Spectra of paracetamol, ibuprofen and caffeine were recorded at several concentrations within their linear ranges and were used to compute the calibration mixture between wavelengths 200 and 400 nm at an interval of 1 nm in methanol:0.1 HCl (3:1). Partial least squares regression (PLS), genetic algorithm coupled with PLS (GA-PLS), and principal component-artificial neural network (PC-ANN) were used for chemometric analysis of data and the parameters of the chemometric procedures were optimized. The analytical performances of these chemometric methods were characterized by relative prediction errors and recoveries (%) and were compared with each other. The GA-PLS shows superiority over other applied multivariate methods due to the wavelength selection in PLS calibration using a genetic algorithm without loss of prediction capacity. Although the components show an important degree of spectral overlap, they have been determined simultaneously and rapidly requiring no separation step. These three methods were successfully applied to pharmaceutical formulation, capsule, with no interference from excipients as indicated by the recovery study results. The proposed methods are simple and rapid and can be easily used in the quality control of drugs as alternative analysis tools.

Bacterial survey of well water--Tehran, Iran.

One hundred twenty-one wells throughout the city of Tehran were monitored during the four seasons of the year for the presence of bacterial indicators of fecal pollution. None of the sites monitored was connected to Tehran's main water distribution system but represented drinking water sources for small communities, individual factories, hospitals, etc. Only 17 samples showed no indication of fecal bacterial contamination throughout the study. The remaining sites were positive for at least one of the following at some season of the year: Escherichia coli, Shigella sp., Citrobacter sp., Klebsiella-Enterobacter group, Clostridium perfringens, or Streptococcus faecalis.

Survey of chemical constituents of Tehran's groundwater.

One hundred and forty wells throughout the City of Tehran and its environs were sampled to determine the chemical quality of the groundwater. Total alkalinity, pH, conductivity, total dissolved solids, hardness and detergent concentrations were determined as well as levels of bicarbonate, calcium, magnesium, sulphate, chloride, sodium, potassium, fluoride, iodide and nitrate. Generally, chemical pollution of the water supplies was low. There were, however, regional elevations in nitrate, chloride and fluoride. Elevated fluoride levels were primarily in the northern regions of the city while high nitrates and chlorides were found primariiy in industrial areas. The health implications of chemical constituents in drinking water are discussed.

Accumulation of cadmium, mercury and lead by vegetables following long-term land application of wastewater.

Several vegetable species which are part of the daily diet of Tehran's population were examined for potential uptake of cadmium, mercury and lead from soil following longterm land application of wastewater. The three study sites located in the south of Tehran have been receiving untreated domestic wastewater by flood irrigation for many years. Elevated levels of cadmium, mercury and lead were found in the upper layers of soil. Examined vegetables accumulated some cadmium, mercury and lead from treated soils, but accumulation was relatively low. Due to the low concentration of these metals and their poor absorption from the gastrointestinal tract (excluding absorption of lead in children), it does not appear that the short-term consumption of these contaminated vegetables would produce acute toxicity. However, since absorption of dietary lead in children is relatively high and children are very sensitive to lead toxicity, short-term consumption of these vegetables plus other environmental sources of these metals in Tehran may produce chronic effects in children.

Trace metal uptake by garden herbs and vegetables.

In many regions of Iran, crops are irrigated with municipal and industrial wastewater that contain a variety of metals. The purpose of this study was to simulate the level of metals that may be presented to plants over a growing season in a controlled laboratory setting. Cadmium, lead, arsenic, chromium, mercury, nickel, copper, zinc, and selenium were applied to plants at the high rate of 200 g metal/ha/wk. The following plants were examined for metal accumulation and effects on yield: garden cress (Lipidium sativum), leek (Allium porrum L.), basil (Ocimum basilicum L.), mint (Mentha arvensis L.), onion (Allium capa L.), radish (Raphanus sativus L.), and tarragon (Artemisia draculus L.). All plants showed significant uptake of all metals when compared to control (p=0.05), and growth was significantly reduced (p=0.05). Cadmium and chromium levels of 85±7.4 and 47.6±8.9 µg/g); selenium levels were highest in tarragon (16.5±5.8 µg/g). Zinc levels were similar (p=0.05) in all species tested, as were mercury and lead. The remaining metals (nickel and copper) showed significant differences in uptake, depending on plant species.

Fate of sodium arsenate in dairy sheep and goats.

This study followed the uptake, distribution, and elimination of sodium arsenate administered in a single dose and in multiple doses, respectively, to Iranian dairy sheep and goats. In the single dosing study, the blood concentration data fit an open two-compartment model of the form:C b (t)=-(A+B)e (-kat) +Ae (-αt) +Be (-ßt) Absorption distribution and elimination rate constants were statistically significantly different for the two animal species. In the multiple dosing study, arsenic accumulated in the blood of both animal species, as expressed by a one compartment model of the form:C t =C ss (1-e (-kt) ) Arsenic was eliminated rapidly at the termination of dosing, with the blood washout half-life being shorter in sheep than in goats. Urinary excretion was the major elimination route from the body of both species.

Uptake, distribution and elimination of monosodium methanearsonate following long term oral administration of the herbicide to sheep and goats.

The rate and extent of accumulation and washout of arsenic, during daily oral administration of the herbicide monosodium methanearsonate (MSMA) were evaluated in Iranian dairy sheep and goats. Subjects received a dose of 10 mg of MSMA as arsenic per kg of body weight daily for 28 consecutive days. The total arsenic concentration in blood and milk was measured during and after the period of MSMA administration while arsenic in urine and feces was measured for 10 days following administration of last dosage of MSMA. Arsenic was accumulated slowly during 28 days of MSMA administration and steady states were essentially complete in sheep after 20 days and in goats following 25 days of MSMA administration. Blood arsenic concentration decreased rapidly after termination of MSMA administration. In both test animals, the half-lives of washout were smaller than accumulation. The concentration of arsenic in the urine and feces of both species did not increase significantly over controls and animals were free of arsenic relatively shortly after administration stopped. These data indicate that arsenic from MSMA is mainly absorbed from gastrointestinal tract and is not significantly accumulated in the body. Arsenic is eliminated from body by way of urine and feces with urinary excretion being the most important route.

Distribution and toxicity of monosodium methanearsonate following oral administration of the herbicide to dairy sheep and goats.

Iranian fat-tailed sheep and dairy goats were administered the herbicide monosodium methanearsonate orally at a dose of 10 mg. MSMA (as arsenic) per kg. of body weight. The concentration time curves of MSMA in the blood of sheep and goats followed a first order composite exponential equation of the form: Cb(t) = Ae- alpha t + Be- beta t - C degrees be-kat. Absorption, distribution and elimination of MSMA, therefore, corresponds to an open two-compartment model. Arsenic from MSMA was readily absorbed from gastrointestinal tract and distributed in the body fluids and the various tissues. Approximately 90% of the arsenic was excreted in the urine within 120 hrs and small amounts were also recovered in feces. Arsenic accumulation in the tissues was low and urinary excretion was the most important exit route. Arsenic concentrations in milk were low when compared to the controls, which indicates that arsenic is not excreted in the milk to significant levels. The absorption, distribution and overall elimination rate constants for the two animal species studied were statistically different at the 0.95 level of confidence which indicates that there are apparently differences in MSMA metabolism by sheep and goats.

Biotransformation of the pesticide sodium arsenate.

Biotransformation is an important parameter in assessing the environmental impact and fate of pesticides since metabolites produced may be either more or less toxic than the parent compound. Sodium arsenate (+5 inorganic), the wood preservative and insecticide, may be converted to both inorganic (+3) and organic compounds (-3) by microorganisms in soil, sediment and water bodies. Biotransformation of sodium arsenate was studied in pure cultures of 5 bacterial species using a mineral salt and limited carbon source medium. Arsenate concentrations were 10 microgram/ml and 100 microgram/ml of arsenic respectively. The rate of biodegradation of the parent compound was described by a first order composite exponential equation of the form Ct = C1e-k1t+C2e-k2t. Rates of production of metabolites (arsenite, monomethylarsine, dimethylarsine and trimethylarsine) were described by a first order exponential equation of the form Ct = Co (1-e-kt).

Effect of sodium arsenate on microbial growth in a chemostat.

Microbial transformation of sodium arsenate, the wood preservative and insecticide, is important in assessing the environmental impact of this pesticide. Recent studies using batch culture techniques have shown that arsenate is metabolized to more toxic end products. This study investigated the effect of the chemical on the microbial cells themselves using continuous flow cultures to examine the effect of arsenate on the growth and maintenance requirements of the microbes. Cell yield was lower and maintenance requirements higher at 100 micrograms/ml arsenate than at 10 micrograms/ml indicating a greater expenditure of energy by the cells to maintain homeostasis.