Assay of nitrofurantoin oral suspensions contaminated with 3-(5-nitrofurfurylideneamino)hydantoic acid.

A reversed-phase high-performance liquid chromatographic (HPLC) analysis of oral suspensions for nitrofurantoin (1) and 3-(5-nitrofurfurylideneamino)hydantoic acid (2), an impurity derived from 1, is presented. The concentration of the impurity ranged from 20 to 300 micrograms/mL in several lots of commercial oral suspensions. Conversion of 1 to 2 with citrate buffer, an excipient in the oral suspension, was achieved; selective hydantoin ring cleavage was accomplished in preference to the generally observed cleavage at the azomethine linkage. The hydantoic acid 2 was synthesized and identified by NMR, IR, TLC, and elemental analysis.

Analysis of drug contamination from parabens in theophylline olamine.

Contaminants in a commercial enema sample of theophylline olamine were found to be derived from parabens and ethanolamine. These contaminants, whose presence was characterized by the loss of preservatives and solubilizing agent, were isolated directly from the drug sample and identified. A high-performance liquid chromatographic (HPLC) system was developed to separate completely and to measure quantitatively theophylline, the two impurities, 4-hydroxybenzoic acid and N-(2-hydroxyethyl)-4-hydroxybenzamide, and the remaining parabens. The material balance obtained from the results of quantitative HPLC indicated the formation of these impurities at the expense of parabens. TLC, IR, and UV spectrophotometry and NMR and mass spectrometric analyses were used for identification or for comparisons of the new compound and the known N-(2-hydroxyethyl)benzamide.

Scope of differential UV and differential fluorescence assays for phenothiazines: comparison with official methods.

Operational difficulties have been encountered with many of the official phenothiazine assay procedures in this laboratory. Although some difficulties were corrected, the procedures still lack specificity. Accordingly, the general scope of differential UV and differential fluorescence methods was investigated. These specific methods are facile, reproducible, and applicable to both composite and single-tablet assays.

Volatile organic analysis by direct aqueous injection.

Gas chromatographic environmental analysis by direct aqueous injection (DAI) was studied for 24 volatile organic analytes (VOAs). Internal standardization was used to determine the precision of analysing these compounds by DAI. Aqueous samples were directly introduced to a gas chromatograph using fused-silica, mega-bore capillary column separation with subsequent full-scan ion trap mass spectral detection. Triplicate injections at seven levels of VOA standard solutions over a 10(3) concentration range were performed using an autosampler set up for on-column injection of 0.2 microl. Comparison of single-ion response curves to triple-ion response curves showed that triple-ion quantitation was more sensitive and precise than single-ion quantitation. Of the 24 VOAs determined at the 20 parts per billion (ppb) level, 19 and 20 were detected by the single-ion calibration and triple-ion calibration, respectively. The weighted and non-weighted regression correlation coefficients, r(2), for the 24 responses curves by the two methods, ranged from 0.910 to 0.998, with 76 of 96 being greater than 0.990. Precision, as measured by per cent relative standard deviation, was shown to be best for later eluting compounds and for higher concentrations. Analysis of an environmental sample by DAI was accomplished in 12 min and indicated the presence of benzene at 80 ppb and chlorobenzene at 2 ppm. This demonstrated the feasibility of applying this technique for screening. Several chlorinated benzenes were also detected, establishing the potential for expanding the method to include higher boiling compounds.

Environmental semivolatiles and nonvolatiles analysis by hyphenated spectral techniques.

Environmental sample extracts contain a variety of volatile and nonvolatile organic compounds exhibiting a range of polarities and concentrations. Although gas chromatography/mass spectrometry (GC/MS) is the method of choice thus far for such analyses, this technique used alone cannot adequately characterize the volatiles in such samples and is not amenable to environmental nonvolatiles. A more complete characterization of environmental and hazardous waste samples is required to assess the dangers posed to the nation's groundwater by hazardous waste dumps. Online spectral confirmation by directly linked GC/Fourier transform infrared (FTIR)/MS is shown to provide useful structural information on environmental volatiles in hazardous wastes, even when the analyte's spectrum is not in either spectral database. This information can lead to biological-hazard estimation. The diffuse reflectance Fourier transform infrared (DRIFT) technique, used in conjunction with thermospray MS or fast atom bombardment (FAB) MS, provides confirmed identifications or confirmed compound class assignments of organic nonvolatiles in solid wastes. This is believed to be the first report of spectral confirmation (identification or functionality) of organic volatiles and nonvolatiles in environmental samples.

Environmental applications of gas chromatography/atomic emission detection.

A gas chromatograph/atomic emission detector (GC/AED) system has been evaluated for its applicability to environmental analysis. Detection limits, elemental response factors, and regression analysis data were determined for 58 semivolatile environmental contaminants. Detection limits for injected analytes ranged from 0.17 to 3.0 ng on the hydrogen 486-nm channel, from 1.0 to 5.0 ng on the nitrogen 174-nm channel, from 0.65 to 11.7 ng on the oxygen 777-nm channel, from 0.071 to 3.0 ng on the chlorine 479-nm channel, and from 0.023 to 0.038 ng on the sulfur 181-nm channel. Mean elemental response factors (ERFs) measured on these channels, relative to the carbon 496-nm channel, were hydrogen, 0.084 (mean %RSD = 6.6); nitrogen, 0.246 (mean %RSD = 19); oxygen, 0.459 (mean %RSD = 16); and chlorine, 0.417 (mean %RSD = 3.6). The higher precision obtained for hydrogen and chlorine, relative to that for nitrogen and oxygen, is attributed to the ability to scan these elemental channels in the same GC run as the carbon 496-nm channel (diode array wavelength range limitation of ∼40 nm/run). Mean ERFs of standard compounds were used to determine the molecular formulas of chlorinated hydrocarbons and chlorinated organosulfur compounds in a contaminated environmental soil sample. These formulas are in good agreement with the molecular weights and chlorine isotopic data obtained from low-resolution gas chromatography/mass spectrometry.

Single-laboratory validation of EPA Method 8150 for determination of chlorinated herbicides in hazardous waste.

Method 8150, published in the second edition of Test Methods for Evaluating Solid Waste, Manual SW-846, required optimization, ruggedness testing, linearity determinations, precision tests, bias testing, gas chromatographic/mass spectrometric confirmation, and quality control guidelines for validation of the protocol. This single-laboratory validation, which is applicable to the determination of the herbicides dicamba, silvex, 2,4-D, 2,4-DB, 2,4,5-T, dinoseb, MCPP, MCPA, and dichlorprop in hazardous waste extracts, was completed and is described in this report. Final ruggedness testing of the optimized procedure gave a mean recovery of 89.3% with a standard deviation of 4.3%. Percent relative standard deviations are less than 10 (n = 20, each analyte) over a 10(2) linear range of concentration for MCPP and MCPA and over a 10(3) linear range of concentration for the other target herbicide esters. Instrumental detection limits for electron capture detection and mass spectrometric identity confirmation were determined and found to be matrix-dependent.

Identification of pollutants in a municipal well using high resolution mass spectrometry.

An elevated incidence of childhood cancer was observed near a contaminated site. Trace amounts of several isomeric compounds were detected by gas chromatography/mass spectrometry (GC/MS) in a concentrated extract of municipal well water. No matching library mass spectra were found and Fourier transform IR and NMR analyses were not feasible due to the low concentration of the compounds. Mass peak profiling from selected-ion-recording data (MPPSIRD) provided the sensitivity and scan speed necessary to acquire mass peak profiles at mass resolutions of 10,000 to 20,000 for the molecular ion (M+) and 10 fragment ions as capillary GC peaks eluted. Using a profile generation model (PGM), the elemental composition of the molecular ion was determined from the exact masses and abundances of the M, M + 1 and M + 2 profiles. Fragment ion compositions were determined from their exact masses based on the elements in the molecular ion. Exact mass differences between the molecular and fragment ions corresponded to unique combinations of atoms for the neutral losses. Consequent reduction of the number of possible structures for the fragment ions simplified mass spectral interpretation. After inspecting library mass spectra for smaller molecules, isomeric structures were hypothesized with cyano and alkylcyano groups attached to tetralin. A literature search found such isomers produced by an industrial polymer synthesis. Three isomers in a standard form polymerization of styrene and acrylonitrile provided the same mass spectra and GC retention times as isomers in the extract.

Interim method for determination of volatile organic compounds in hazardous wastes.

An analytical protocol is presented for the determination of volatile organic compounds in hazardous wastes that are amenable to the purge-and-trap method. The protocol features a tetraethylene glycol dimethyl ether (tetraglyme) extraction of the liquid or solid waste, addition of an aliquot of the tetraglyme waste to water, and purging of the tetraglyme-water mixture with subsequent gas chromatographic/mass spectrometric (GC/MS) analysis. The size of the tetraglyme aliquot is determined by gas chromatographic screening of a hexadecane waste extract. Quality assurance/quality control procedures are included within the analytical protocol. Spike extraction recoveries of industrial wastes obtained by following this protocol are given.

Environmental Analysis by ab Initio Quantum Mechanical Computation and Gas Chromatography/Fourier Transform Infrared Spectrometry.

Computational chemistry, in conjunction with gas chromatography/mass spectrometry/Fourier transform infrared spectrometry (GC/MS/FT-IR), was used to tentatively identify seven tetrachlorobutadiene (TCBD) isomers detected in an environmental sample. Computation of the TCBD infrared spectra was performed with the Gaussian quantum chemistry software. The Hartree-Fock/6-31G* level of theory was employed, with IR frequencies scaled by a standard factor of 0.89. This approach shows great promise as a means of characterizing or confirming environmental analyte identifications when standard spectra, or pure standards required to measure standard spectra, are unavailable.