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Nervous system active pharmaceutical ingredients (APIs), including anti-depressants and opioids, are important clinically administered pharmaceuticals within healthcare facilities. This study provides source characterization data describing the composition and magnitude of nervous system APIs present in healthcare facility wastewaters. Concentrations and mass loadings of ten nervous system APIs and three nervous system API metabolites are reported for wastewaters from a hospital, nursing, assisted living, and independent living facility within a single municipality. Concentrations of nervous system APIs ranged from non-detectable levels for alprazolam in all four facility wastewaters to a high of 290 ng/L amitriptyline in nursing facility wastewater. The summed mean concentration of all thirteen analytes ranged from 402 ng/L in independent living facility wastewater to 624 ng/L in assisted living facility wastewater. Wastewater flow rates from each facility were combined with concentration data to estimate the daily mass loading of nervous system APIs leaving each facility through wastewater discharge to the municipal sewer system. The total mass loading of all thirteen analytes for the hospital, nursing, assisted living, and independent living facility was 228, 44, 29.5, and 28.1 mg/day, respectively. The total mass loading of nervous system APIs contributed to the municipality's wastewater from all four facilities was 330 mg/day., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Two simple, precise, and accurate extractive spectrophotometric methods have been developed for the determination of doxepin hydrochloride in pharmaceutical preparations. The methods are based on the formation of ion association complexes of doxepin with titanium (IV) and iron (III) thiocyanate complexes in acidic medium. The produced compounds are insoluble in water but well soluble in some organic solvents. They are extracted with mixtures of butyl alcohol-chloroform (2:3, v/v) and (1:4, v/v) and measured spectrophotometrically at 400 and 490 nm for DOX-Ti-SCN and DOX-Fe(III)-SCN methods, respectively. Beer's law was obeyed in the concentration ranges of 5-50 and 3-30 microg/ml with molar absorptivity of 7.12 x 10(3) and 1.36 x 10(4) l mol(-1) cm(-1) for DOX-Ti-SCN and DOX-Fe-SCN systems, respectively. The proposed methods have been successfully applied for the analysis of the drug in dosage forms. No interference was observed from common pharmaceutical adjuvants. The methods have been also used for the determination of the drug in the presence of its degradation product. Statistical comparison of the obtained results with the reference methods shows excellent agreement and indicates no significant difference in accuracy and precision.

We present the validation of a method using non-aqueous capillary electrophoresis (NACE) for quantitative analysis of four tricyclic antidepressants (TADs) in pharmaceutical formulations and plasma. The method presented high resolution allowing the separation of the TADs in 4.3 min at optimized conditions: 50 mM ammonium acetate, 1 M acetic acid in acetonitrile, capillary with 48 cm in length, 40 cm to the detector, and voltage of 30 kV. Acceptable precision (relative standard deviation R.S.D.14.1% from plasma samples) and linearity were achieved using the internal standard (IS) method. The limits of quantification determined for plasma, after liquid-liquid extraction (LLE), were between 30 and 50 ng ml-1. These values are beyond the plasmatic therapeutic concentration. Our results were found comparable or better than those described in the literature for high performance liquid chromatography (HPLC)-based methods.

Eriochrome cyanine R (ECR) has been tested as reagent for the determination of imipramine. It reacts in neutral medium with imipramine forming reddish compound, which can be quantitatively extracted into n-butanol. This property has been successfully used for the extractive-spectrophotometric determination of imipramine. Beer's law is obeyed in concentration range of 10-80 microg ml(-1) of imipramine. The method was applied to the determination of imipramine in its pharmaceutical.

The use of mathematically enhanced ultraviolet/visible (UV/VIS) absorbance spectral analysis and spectral contrast software techniques in high performance liquid chromatography (HPLC) and micellar electrokinetic capillary electrophoresis (MECC) as an aid for the determination of peak homogeneity, identification, and tracking during method development was investigated. Various structurally similar pharmaceutical compounds, and compounds present as either cis/trans isomers, diastereomers, or enantiomers were used as test compounds to probe the limits of this technique. Two tricyclic antidepressants, nortriptyline and imipramine, were employed to study the effects of HPLC mobile phase composition and pH on the ability to identify and track peaks during method development. It was found that method changes altered the spectral matches used for identification, but not enough to cause incorrect peak identification. It was also shown using HPLC that the cis/trans isomers of doxepin and the diastereomers ephedrine and pseudoephedrine could be distinguished. The mathematically enhanced spectral analysis and spectral contrast software techniques were also employed with MECC. Peaks tracking during method development as pH and the concentration of surfactant changes is shown for a separation of various penicillin type antibiotics. It was shown that during chiral MECC (CMECC) analyses ephedrine/pseudoephedrine diastereomers as well as ephedrine enantiomers could be distinguished. The determination of enantiomers is possible in CMECC since enantiomers are eluted as diastereomeric complexes, as opposed to HPLC where they are eluted in their native state.

In a random group of medical examiner cases, muscle tissue, as well as blood and vitreous humor, was analyzed for ethyl alcohol, and the results were compared. When the blood concentration was greater than 0.10 g/dL, the muscle to blood ratio was 1.00 or less (average 0.94), and when the blood concentration was less than 0.10 g/dL, this ratio was greater than 1.00 (average 1.48). The author proposes that this ratio is dependent upon the time course of absorption and distribution, as has been observed for vitreous humor, but with a more rapid equilibration. Muscle tissue was also analyzed in another group of cases found to be positive for one or more drugs in blood. The concentrations of the drugs in muscle varied from none detected to 6.5 times those in blood and seemed to be dependent on the time course between ingestion and death, as well as on the nature of the drug. For most common basic drugs, the ratios were often near unity. Muscle is proposed as a useful alternative specimen to postmortem blood.

There is an increasing need for sensitive and specific methods for toxicological screening. Development of a dual-column gas chromatography system for the screening of drugs and metabolites in the plasma of poisoned patients is described. The system has been evaluated using plasma from a well-documented series of patients presenting with overdose, and results obtained have been compared with results of specific assays for the groups of drugs encountered. The method has been found to be of value in the treatment of poisoned patients despite its apparent insensitivity to certain more polar drug metabolites such as nortriptyline and desmethyldiazepam.

Photon correlation spectroscopy (PCS) has been used to examine the aggregation in aqueous NaCl solution of a series of antidepressant and antihistamine drugs (hydrochlorides of imipramine, clomipramine, amitriptyline, butriptyline, protriptyline, doxepin, dothiepin, iprindole, diphenhydramine, bromodiphenhydramine, orphenadrine) propranolol hydrochloride and propantheline bromide. Critical micelle concentrations were measured by surface tension and PCS. Micellar sizes were investigated as functions of drug structure and drug and NaCl concentration. Generally, antidepressants formed the largest micelles. We propose that the antidepressants aggregate in a similar fashion to the phenothiazines by stacking with size increasing by addition of single monomers to stacks and by addition of more stacks to the aggregate.

The usefulness of amperometric detection in pharmaceutical analyses was investigated for different groups of drugs. The UV response at 254 nm and that at the absorption maximum of the solute were compared with the electrochemical signal obtained. The minimum detectable concentration (nanograms on-column) of each substance is reported for the three different detection systems. This comparison was performed for 72 drugs (local anaesthetics, antipyretics, tricyclic antidepressants, sulphonamides, sex hormones, beta-adrenoceptor blocking agents, phenothiazines, alkaloids, diuretics and penicillins). The median limit of detection of the amperometric detector (see definition in the text) is 1.0 ng on-column and the median gain in sensitivity, compared with UV detection is 22.5.