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Analysis of residual quantities of contaminants in foods of animal origin is crucial for quality control of consumer products. This study was aimed to develop a simple and raid analytical method for detection of tetramisole and diethylcarbamazine using gradient liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). Tetramisole, diethylcarbamazine, and guaifenesin (as an internal standard) were extracted from milk, eggs, and porcine muscle using acetonitrile followed by partitioning at -20 °C for 1h. No extract purification was deemed necessary. The analytes were separated on C18 column using ammonium formate both in water and methanol. Good linearity was achieved over the tested concentration range with R(2) ⩾ 0.974. Recovery at two fortification levels ranged between 67.47% and 97.38%. The intra- and inter-day precisions were <20%. The limit of quantification was 0.2 and 2 ng/g for tetramisole and diethylcarbamazine, respectively. An analytical survey of samples purchased from large markets showed that none of the samples contained any of the target analytes. To the best of our knowledge, this is the first report on the quantitative determination of tetramisole and diethylcarbamazine in animal food products.

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One titrimetric and two spectrophotometric methods are proposed for the determination of diethylcarbamazine citrate (DEC) in bulk drug and in formulations using potassium iodate and potassium iodide as reagent. The methods employ the well-known analytical reaction between iodate and iodide in the presence of acid. In titrimetry (method A), the drug was treated with a measured excess of thiosulfate in the presence of unmeasured excess of iodate-iodide mixture and after a standing time of 10 min, the surplus thiosulfate was determined by back titration with iodine towards starch end point. Titrimetric assay is based on a 1:3 reaction stoichiometry between DEC and iodine and the method is applicable over 2.0-10.0 mg range. The liberated iodine is measured spectrophotometrically at 370 nm (method B) or the iodine-starch complex measured at 570 nm (method C). In both methods, the absorbance is found to be linearly dependent on the concentration of iodine, which in turn is related to DEC concentration. The calibration curves are linear over 2.5-50 and 2.5-30 µg mL-1 DEC for method B and method C, respectively. The calculated molar absorptivity and Sandell sensitivity values were 6.48×103 L mol-1 cm-1 and 0.0604 µg cm-2, respectively, for method B, and their respective values for method C are 9.96×103 L mol-1 cm-1 and 0.0393 µg cm-2. The intra-day and inter-day accuracy and precision studies were carried out according to the ICH guidelines. The methods were successfully applied to the analysis of DEC formulations.

Propõem-se titulação e dois métodos espectrofotométricos para a determinação de citrato de dietilcarbamazina (DEC) a granel e em suas formulações, usando iodato de potássio e iodeto de potássio como reagente. Os métodos utilizam a reação analítica conhecida entre iodato e iodeto, na presença de ácido. Na titulometria (Método A), o fármaco foi tratado com excesso medido de tiossulfato, na presença de excesso não medido de mistura iodato-iodeto e, depois de um tempo de repouso de 10 min, o excesso de tiossulfato foi determinado por titulação de retorno com iodo até o ponto final com amido. A titulação é baseada em reação com estequiometria 1:3 entre DEC e iodo e o método é aplicável na faixa de 2.0-10.0 mg. O iodo liberado é medido espectrofotometricamente a 370 nm (método B) ou o complexo de iodo-amido medido a 570 nm (método C). Em ambos os métodos, a absorvância é considerada linearmente dependente da concentração de iodo, a qual, por sua vez, está relacionada à concentração de DEC. As curvas de calibração são lineares para concentrações de DEC de 2.5-50 e 2.5-30 mg mL- 1 para o método B e para o método C, respectivamente. A absortividade molar calculada e os valores de sensibilidade Sandel foram 6.48×103 L mol-1 cm- 1 e 0.0604 ug cm-2, respectivamente, para o método B, e os seus respectivos valores para o método C são 9.96×103 L mol-1 cm-1 e 0.0393 mg cm-2. Os estudos de exatidão e precisão intra-dia e inter-dia foram realizados de acordo com as diretrizes da ICH. Os métodos foram aplicados com sucesso na análise de formulações de DEC.

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The World Health Organization has called for an effort to eliminate Lymphatic Filariasis (LF) around the world. In regions where the disease is endemic, local production and distribution of medicated salt dosed with diethylcarbamazine (DEC) has been an effective method for eradicating LF. A partner of the Notre Dame Haiti program, Group SPES in Port-au-Prince, Haiti, produces a medicated salt called Bon Sel. Coarse salt is pre-washed and sprayed with a solution of DEC citrate and potassium iodate. Iodine levels are routinely monitored on site by a titrimetric method. However, the factory had no method for monitoring DEC. Critical analytical issues include 1) determining whether the amount of DEC in each lot of Bon Sel is within safe and therapeutically useful limits, 2) monitoring variability within and between production runs, and 3) determining the effect of a common local practice (washing salt before use) on the availability of DEC. This paper describes a novel titrimetric method for analysis of DEC citrate in medicated salt. The analysis needs no electrical power and requires only a balance, volumetric glassware, and burets that most salt production programs have on hand for monitoring iodine levels. The staff of the factory used this analysis method on site to detect underloading of DEC on the salt by their sprayer and to test a process change that fixed the problem.

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Reclaimed wastewater is an important source of irrigation in semiarid and arid zones. Here we report data on carbamazepine (CBZ) uptake by cucumber plants in hydroponic culture and greenhouse experiments using different soil types irrigated with fresh water or reclaimed wastewater. Data obtained from the hydroponic culture experiments suggest that CBZ is mainly translocated by water mass flow, and thus it is concentrated and accumulated to the largest extent in the mature/older leaves. Carbamazepine concentration in cucumber fruits and leaves was negatively correlated with soil organic matter content. The concentrations of CBZ in the roots and stems were relatively low, and most CBZ in the plant (76-84% of total uptake) was detected in the leaves. A greenhouse experiment using fresh water and reclaimed wastewater spiked, or not, with CBZ at 1 µg L(-1) (typical concentration in effluents) revealed that CBZ can be taken up and bioaccumulated from its background concentration in reclaimed wastewater. Bioaccumulation factor (calculated as the ratio of CBZ concentration in the plant to that in the soil solution) for the fruits (0.8-1) was significantly lower than the value calculated for the leaves (17-20). This study emphasizes the potential uptake of active pharmaceutical compounds by crops in organic-matter-poor soils irrigated with reclaimed wastewater and highlights the potential risks associated with this agricultural practice.

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In 1997, the World Health Organization (WHO) made a commitment to eliminate lymphatic filariasis. The WHO Global Program to Eliminate Lymphatic Filariasis (WHO-FIL) needed a reliable supply of diethylcarbamazine citrate (DEC) of known acceptable quality at an affordable price, so in August 1999, it started the DEC Project. Today's standards required development of a modern stability-indicating assay method for DEC and for DEC tablet dissolution. ADD Advanced Drug Delivery Technologies (Switzerland) developed a high-pressure liquid chromatography assay, which was independently validated and is in the United States Pharmacopoeia 25 (2002). After a global search, the project found that almost all existing and potential DEC active pharmaceutical ingredient (API) and tablet manufacturers are in low-income countries. The project constructed an audit team to conduct on-site audits to assess good manufacturing practices according to European Union standards. National/state inspectors accompany the audit team. The team prequalified one DEC API manufacturer and three DEC tablet manufacturers. The project plans to increase the number of prequalified DEC manufacturers. Now, WHO-FIL only purchases from prequalified manufacturers. Consolidation of several national program DEC requirements into a limited international competitive bid reduced the price for DEC tablets between 30% and 45%, compared to previous small-scale WHO purchases.

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A simple and reproducible method for the estimation of diethylcarbamazine citrate (DEC) by high performance liquid chromatography (HPLC) in DEC-medicated salt was developed. HPLC analysis was conducted with a mobile phase containing acetonitrile/phosphate buffer (20 mM KH(2)PO(4,) adjusted to pH 3.2 with 10% ortho-phosphoric acid) in the ratio of 1:9 and at a flow rate of 1.5 ml/min. A Phenomenex C8 column (15 cmx4.6 mm) of 5 microm particle size was used for the analysis. Analysis was done at UV 210 nm, 0.02 a.u.f. and 40 degrees C. The coefficient of variation was <10% in the range of 1-25 microg/ml and the minimum detectable level was 0.5 microg/ml. The quality of DEC-medicated salt prepared by two methods was analyzed by using the HPLC method. In spray drying method, 29 and 71% of the samples and in rotating drum method, 9 and 12% of samples were found to contain DEC at 0.15-0.25% and >0.25%, respectively. Thus, this quick and simple HPLC method for the estimation of DEC could play a vital role in checking the quality of the DEC medicated salt used for the control of filariasis.

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Piperazine, piperazine salts, and piperazine-containing compounds, e.g., diethylcarbamazine and piperazine theophylline, are determined by direct current polarography of the corresponding nitroso-derivative. The nitroso-derivative exhibits a well defined cathodic wave at -0.8 V vs SCE. The plot of peak height vs concentration is rectilinear between 1.6 X 10(-5) and 19.2 X 10(-5) M. Recoveries from bulk drugs were 97.7-101.12% with a standard deviation of 2.14-3.44. The procedure was successfully applied to analysis of drug content in representative dosage forms with good accuracy.

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