Acid Degradation Products Research Articles

Investigation of sorbic acid volatile degradation products in pharmaceutical formulations using static headspace gas chromatography

An analytical method that allows simultaneous analysis of sorbic acid and its degradation products was developed using static headspace gas chromatography (HS-GC). AT-Aquawax-DA, the capillary column used, showed good selectivity and separation towards sorbic acid and its degradation products. Sorbic acid degradation was investigated in both acidic and aqueous media at room and elevated temperatures. In total 12 sorbic acid degradation products were found, 8 of which could be characterized. The method was investigated for its accuracy towards estimation of degradation products. Using the HS-GC method different batches of pharmaceutical preparations such as cold cream, cetomacrogol cream and vaseline were investigated for sorbic acid degradation products which were estimated by applying the standard addition method. Acetaldehyde was found to be the major degradation product. The other identified degradation products were: acetone; 2-methylfuran; crotonaldehyde; alfa-angelicalactone; 2-acetyl, 5-methylfuran; toluene and 2,5-dimethylfuran. Both mass spectrometeric (MS) and flame ionization detection (FID) were used. The qualitative investigation was done on HS-GC–MS and the quantitative work on HS-GC–FID.

Synthesis and Structure Determination of Covalent Conjugates Formed from the Sulfury−Roasty-Smelling 2-Furfurylthiol and Di- or Trihydroxybenzenes and Their Identification in Coffee Brew

Recent investigations demonstrated that the reaction of odor-active thiols such as 2-furfurylthiol with thermally generated chlorogenic acid degradation products is responsible for the rapid aroma staling of coffee beverages. To get a clear understanding of the molecular mechanisms underlying this aroma staling, the existence of putative phenol/thiol conjugates needs to be verified in coffee. The aim of the present study was therefore to synthesize such conjugates for use as reference substances for LC-MS screening of coffee. To achieve this, catechol, 3-methyl-, 4-methyl-, and 4-ethylcatechol, pyrogallol, hydroxyhydroquinone, 5-O-caffeoylquinic acid, and caffeic acid, respectively, were reacted with 2-furfurylthiol in the presence of iron(III) chloride and air oxygen. After purification, the structures of 25 phenol/thiol conjugates were identified by means of LC-MS/MS and 1D/2D NMR experiments. Using these compounds as reference materials, four conjugates, namely, 3-((2-furylmethyl)sulfanyl)catechol, 3-((2-furylmethyl)sulfanyl)-5-ethylcatechol, 4-((2-furylmethyl)sulfanyl)hydroxyhydroquinone, and 3,4-bis((2-furylmethyl)sulfanyl) hydroxyhydroquinone, were identified for the first time in coffee brew by means of HPLC-MS/MS(MRM). These findings clearly demonstrate catechol, 4-ethylcatechol, and hydroxyhydroquinone as the primary thiol trapping agents involved in the aroma staling of coffee beverages.

Simultaneous separation and determination of process-related substances and degradation products of venlafaxine by reversed-phase HPLC

A simple and rapid gradient RP HPLC method for simultaneous separation and determination of venlafaxine and its related substances in bulk drugs and pharmaceutical formulations has been developed. As many as four process impurities and one degradation product of venlafaxine have been separated on a Kromasil KR100-5C18 (4.6 mm x 250 mm; particle size 5 microm) column with gradient elution using 0.3% diethylamine buffer (pH 3.0) and ACN/methanol (90:10 v/v) as a mobile phase. The column was maintained at 40 degrees C and the eluents were monitored with photo diode array detection at 225 nm. The chromatographic behaviour of all the compounds was examined under variable compositions of different solvents, temperatures, buffer concentrations and pH. The method was validated in terms of accuracy, precision and linearity as per ICH guidelines. The inter- and intraday assay precision was < 4.02% (%RSD) and the recoveries were in the range of 96.19-101.14% with %RSD < 1.15%. The correlation coefficients (r2) for calibration curves of venlafaxine as well as impurities were in the range of 0.9942-0.9999. The proposed RP-LC method was successfully applied to the analysis of commercial formulations and the recoveries of venlafaxine were in the range of 99.32-100.67 with %RSD <0.58%. The method could be of use not only for rapid and routine evaluation of the quality of venlafaxine in bulk drug manufacturing units but also for the detection of its impurities in pharmaceutical formulations. Forced degradation of venlafaxine was carried out under thermal, photo, acidic, basic and peroxide conditions and the acid degradation products were characterized by ESI-MS/MS, 1H NMR and FT-IR spectral data.

Reassignment of the Configuration of Salvianolic Acid B and Establishment of Its Identity with Lithospermic Acid B

Salvianolic acid B and lithospermic acid B are the major components of Salvia miltiorrhiza, which is one of the most popular herbal traditional medicines in Asian countries. Salvianolic acid B and lithospermic acid B are reported to have identical structures except for the configurational assignments of two stereocenters. Through chemical correlation between a degradation product of salvianolic acid B and synthetic material, the absolute configuration of salvianolic acid B has been corrected to establish that salvianolic acid B and lithospermic acid B are in fact the same compound.

Study of Precursors Responsible for Off-Flavor Formation during Storage of Potato Flakes

Off-flavors frequently appear during the storage of potato flakes. Volatile profile analysis performed by solid-phase microextraction-gas chromatography-mass spectrometry revealed that hexanal is the main compound that appears during the storage period. Hexanal may be a degradation product of linoleic acid formed through linoleic acid hydroperoxide cleavage. Profiles of hexanal precursors were determined from potato flakes at different storage time points. Linoleic acid-derived oxylipins are predominant in potato flakes. The free oxylipins identified, in descending order, are as follows: hexanal, hydroxy polyunsaturated fatty (PUFAs), oxo PUFAs, divinyl ether PUFAs, and hydroperoxy PUFAs. However, the main oxylipins detected were esterified: esterified hydroxy, hydroperoxy, and oxo PUFAs. Oxylipins reveal different evolutions during the storage period. Chiral high-performance liquid chromatography analysis of the precursors of hexanal and other oxylipins revealed a racemic composition that supports the nonenzymatic formation of hexanal and most of the other oxylipins identified.

Synthesis, polymerisation and degradation of poly(lactide-co-propylene glycol) dimethacrylate adhesives

Fluid ABA triblock poly(lactide-co-propylene glycol-co-lactide)s with 7, 17 or 34 propylene glycol and 2, 4, or 8 lactic acid units in each B and A block, respectively, end capped with methacrylate groups were prepared and polymerisation rates upon blue light exposure for 60, 120 or 240 s using 0.5, 1 or 2 wt.% initiators determined. The shortest monomer formulation, with 0.5 wt.% initiators, was most promising as an injectable degradable adhesive for biomedical applications, achieving 96% polymerisation by 120 s after the start of 60 s illumination, forming then a semi-rigid polymer that in water released linearly with time poly(methacrylic-co-lactic) acid degradation products. Over 14 weeks, 2 mm thick specimens largely maintained their dimensions as water sorption balanced the 19 wt.% material loss. Raising initiator concentration or monomer length reduced polymerisation rate on the lower surface of samples. Increasing the number of lactic acid units in each A block from 2 to 8 also enhanced photocrosslinked polymer water sorption and increased average total mass loss to 60 wt.% over 14 weeks but acid product release rate decreased with time. Monomers produced with longer polypropylene glycol B blocks required longer periods of light exposure for full cure and the final polymers exhibited slower non-linear hydrolytic degradation.

Stability Indicating Methods for the Determination of Some Fluoroquinolones in the Presence of Their Decarboxylated Degradates

Two stability-indicating methods, namely densitometric TLC and derivative spectrophotometry for the determination of the fluoroquinolone antibacterials lomefloxacin (Lfx), moxifloxacin (Mfx), and sparfloxacin (Sfx) in the presence of their acid degrades are described. Acid degradation was adopted and the main decarboxylated product separated by TLC. Degradation products were identified confirming a previously mentioned degradation scheme. The densitometric method is based on the separation of the intact drug from its acid degradation product on silica gel G plates using different mobile phases and the spots of the intact drugs were scanned at 288, 290, and 292 nm for Lfx, Mfx, and Sfx, respectively. The derivative spectrophotometric method utilizes first derivative D(1) UV spectrophotometry with zero crossing points at 295.2 nm for Lfx, 280.4 and 303.4 nm for Mfx, and 280.8 nm for Sfx. Regression analysis of Beer's plots showed good correlation in the concentration ranges 0.2-1.2, 0.1-1.4, and 0.5-2.0 microg/spot for Lfx, Mfx, and Sfx, respectively, in the densitometric method and 2-16 microg/ml for all drugs in the derivative spectrophotometric method. The proposed methods were successfully applied for the determination of the investigated drugs in bulk powder with mean percentage accuracy ranges from 98.93 to 101.25% for the TLC method and from 98.18 to 100.35% for the D(1) method. The proposed methods were also applied for the determination of the investigated drugs in their pharmaceutical dosage forms and their validity was assessed using the standard addition technique with mean percentage recovery ranging from 100.25 to 101.70% in the TLC method and from 99.27 to 102.12% in the D(1) method. The selectivity of the proposed methods was tested by the analysis of laboratory-prepared mixtures containing different percentages of the studied drugs and their acid degrades. The proposed methods were found selective for the determination of the intact drugs in the presence of up to 90% of their degrades in the TLC method and 70% for Lfx and 90% for Mfx and Sfx in the D(1) method.

Uric acid, a nucleic acid degradation product, down-regulates dsRNA-triggered arthritis

Uric acid, the naturally occurring degradation product of purine metabolism, is a danger signal, driving maturation of dendritic cells. It is well known that uric acid crystals display potent proinflammatory properties--the cause of gout--whereas the biological properties of soluble uric acid are less well documented. We have demonstrated previously that nucleic acids of endogenous and exogenous origin display proinflammatory properties. The aim of the present study was to assess the impact of soluble uric acid on in vivo inflammatory responses. Mice were administered with uric acid suspension in saline or saline alone prior to induction of neutrophil-mediated inflammation, delayed-type hypersensitivity, histamin-induced edema (measure of vasodilation capacity), as well as double-stranded (ds)RNA-triggered arthritis. Frequency and severity of arthritis were decreased significantly in mice exposed to dsRNA and simultaneously treated with uric acid as compared with saline-treated controls. Also, granulocyte-mediated inflammatory response and vasodilation capacity were reduced significantly in mice treated with uric acid as compared with their control group. The data suggest that down-regulation of inflammation was mediated by skewing the inflammatory response from the peripheral sites to the peritoneal cavity and down-regulating vasodilatatory capacity and thereby affecting leukocyte migration. In contrast, the T cell-mediated delayed-type hypersensitivity reaction was not affected significantly in mice exposed to uric acid. These findings demonstrate that uric acid displays a potent, distant anti-inflammatory effect in vivo. This property seems to be mediated by down-regulation of neutrophil influx to the site of inflammatory insult.

High-performance liquid chromatography method for simultaneous determination of aliphatic acid, aromatic acid and neutral degradation products in biomass pretreatment hydrolysates

A variety of degradation products are produced upon dilute acid pretreatment of lignocellulosic biomass. Within this larger construct, organic acids, phenols and aromatic aldehydes represent important compound classes to investigate due to increasing evidence of their inhibitory effect on fermentative microorganisms. An analytical extraction procedure is presented, enabling isolation of potential analytes away from alternative products in biomass hydrolysates. Additionally, a reversed-phase high-performance liquid chromatography (HPLC) method has been developed and validated, affording simultaneous separation and quantitative determination of 32 potential analytes in water with UV detection at 210 nm. The method was subsequently employed to quantify a variety of aliphatic acid, aromatic acid, aldehyde and phenolic degradation products in a corn-stover hydrolysate at concentration levels ranging from 0.02 to 41 mM.

Quantification of urinary allantoin by capillary zone electrophoresis during recombinant urate oxydase (rasburicase) therapy

Objectives: Rasburicase (Fasturtec®) is used to prevent or treat hyperuricemia associated with chemotherapy. We developed a capillary zone electrophoresis method to measure urinary allantoin, the degradation product of uric acid by rasburicase. Design and methods: Electrophoresis was performed using a P/ACE 5500 system (Beckman) with a fused silica capillary tube and a UV–visible detector set at 214 nm. Urine samples from 10 patients with non-Hodgkin’s lymphoma were analyzed to validate the technique. Results: Using a sodium tetraborate running buffer, urinary allantoin was separated from related compounds and internal standard in less than 30 min. The method was linear up to 1.25 g/L (quantification limit: 30 mg/L); precision was below 10%. The total amount of allantoin excreted in patients treated by rasburicase ranged from 1.5 g to 7.9 g/4 days. Conclusion: This CZE assay is a simple, rapid and reproducible method to measure allantoin in urine. Different elimination profiles have been found in patients treated with rasburicase.

Pulse radiolysis study of the interaction of retinoids with peroxyl radicals

Vitamin A (retinol) and its derivatives—retinal and retinoic acid—are known for their ability to inhibit lipid peroxidation. Antioxidant actions of retinoids have been attributed to chain-breaking by scavenging of peroxyl radicals. Based on chemical analysis of retinoic acid degradation products formed during microsomal lipid peroxidation, it was previously suggested that retinoids interact with peroxyl radicals forming free carbon-centered radical adducts. However, it can be argued that such a mode of antioxidant action of retinoids is not sufficient to fully explain their effectiveness at inhibiting lipid peroxidation, which in many systems is comparable to, or even exceeds, that of α-tocopherol. In order to elucidate the mechanism of interaction of retinoids with peroxyl radicals, (trichloromethyl)peroxyl radical was generated by pulse radiolysis, and its interactions with retinoids solubilized in Triton X-100 micelles were followed by kinetic absorption spectroscopy. All retinoids—retinol, retinal, and retinoic acid—interacted with the peroxyl radical, and at least two transient products were detected. One of these products, absorbing at 590 nm, was identified as retinoid cation radical. Therefore, we postulate that, apart from formation of radical adducts, retinoids may also scavenge peroxyl radicals by electron transfer.

A pH-Stability Study of Phoslactomycin B and Analysis of the Acid and Base Degradation Products

Phoslactomycin B (PLM-B), a potent and selective inhibitor of serine threonine phosphatase is of interest for its antitumor, antifungal and antiviral activity. Described herein is an evaluation of the solution stability of phoslactomycin B at various pH and temperature conditions. Phoslactomycin B was produced from a NPI mutant strain of Streptomyces sp. HK-803 and purified by semi-preparative HPLC. A study of PLM-B degradation was carried out in the pH range of 2 approximately 10 at 30 degrees C and 50 degrees C using an HPLC assay. The PLM-B decomposition was observed to exhibit a U-shaped pH profile and demonstrated both acid and base-catalyzed decomposition. The decomposition could be described by the equation kOBS=kH x 10(-PH) + kOH x 10(pH-14) (kH=45 +/- 7 M(-1) h (-1); kOH= 448+/-73 M(-1h)(-1). PLM-B was found to be most stable at pH 6.63. The major acid and base products were separated and purified. Mass spectroscopic and NMR analysis revealed hydrolysis of the alpha, beta-unsaturated lactone provided the major degradation product under base conditions. Two other products in which hydration of the alpha, beta-unsaturated double bond preceded hydrolysis or methanolysis of the lactone were obtained. Under acidic condition MS and NMR analysis revealed that a dehydration step provided a C9-C11 phosphorinane derivative of PLM-B as one of the major products. The remaining acid degradation products were shown to be mixture of various dehydration products containing an additional double bond in central core of the PLM-B carbon skeleton. The major acid and base degradation products had dramatically reduced antifungal activity despite retaining the same structural core.

Snake venom hyaluronidase: a therapeutic target

The diffusion of toxins from the site of a bite into the circulation is essential for successful envenomation. Degradation of hyaluronic acid in the extracellular matrix (ECM) by venom hyaluronidase is a key factor in this diffusion. Hyaluronidase not only increases the potency of other toxins but also damages the local tissue. In spite of its important role, little attention has been paid to this enzyme. Hyaluronidase exists in various isoforms and generates a wide range of hyaluronic acid degradation products. This suggests that beyond its role as a spreading factor venom hyaluronidase deserves to be explored as a possible therapeutic target for inhibiting the systemic distribution of venom and also for minimizing local tissue destruction at the site of the bite.

Revisiting quorum sensing: Discovery of additional chemical and biological functions for 3-oxo- N -acylhomoserine lactones

Bacteria use small diffusible molecules to exchange information in a process called quorum sensing. An important class of autoinducers used by Gram-negative bacteria is the family of N-acylhomoserine lactones. Here, we report the discovery of a previously undescribed nonenzymatically formed product from N-(3-oxododecanoyl)-L-homoserine lactone; both the N-acylhomoserine and its novel tetramic acid degradation product, 3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione, are potent antibacterial agents. Bactericidal activity was observed against all tested Gram-positive bacterial strains, whereas no toxicity was seen against Gram-negative bacteria. We propose that Pseudomonas aeruginosa utilizes this tetramic acid as an interference strategy to preclude encroachment by competing bacteria. Additionally, we have discovered that this tetramic acid binds iron with comparable affinity to known bacterial siderophores, possibly providing an unrecognized mechanism for iron solubilization. These findings merit new attention such that other previously identified autoinducers be reevaluated for additional biological functions.

In vitro degradation of porous degradable and bioactive PHBV/wollastonite composite scaffolds

In vitro degradation of three-dimensional composite scaffolds made from poly(3-hydroxybutyrate- co-3-hydroxyvalerate) (PHBV) and wollastonite has been investigated up to 15 weeks in phosphate buffered saline (PBS) solution at 37 °C. Weight loss, water absorption, pH of the PBS and molecular weight measurements were used to monitor the degradation of the scaffolds. The results showed that the addition of wollastonite into PHBV scaffolds resulted in an increase of the water absorption and weight loss as compared to that of the pure PHBV scaffolds. However, the polymer molecular weight in the pure PHBV scaffolds was found to decrease more rapidly than that of the PHBV in the composite scaffolds. This delayed degradation in the composite scaffolds was caused probably by the dissolution of alkaline ions from the wollastonite, which resulted in a buffering effect to the acidification of the PBS due to the acid degradation products of PHBV. These results suggested that the addition of wollastonite into polymer might be a useful method to adjust the degradation rate of the composite scaffolds for special applications in tissue engineering.

Correlation of Mass Spectrometry Identified Bacterial Biomarkers from a Fielded Pyrolysis-Gas Chromatography-Ion Mobility Spectrometry Biodetector with the Microbiological Gram Stain Classification Scheme

A pyrolysis-gas chromatography-ion mobility spectrometry (Py-GC-IMS) briefcase system has been shown to detect and classify deliberately released bioaerosols in outdoor field scenarios. The bioaerosols included Gram-positive and Gram-negative bacteria, MS-2 coliphage virus, and ovalbumin protein species. However, the origin and structural identities of the pyrolysate peaks in the GC-IMS data space, their microbiological information content, and taxonomic importance with respect to biodetection have not been determined. The present work interrogates the identities of the peaks by inserting a time-of-flight mass spectrometry system in parallel with the IMS detector through a Tee connection in the GC module. Biological substances producing ion mobility peaks from the pyrolysis of microorganisms were identified by their GC retention time, matching of their electron ionization mass spectra with authentic standards, and the National Institutes for Standards and Technology mass spectral database. Strong signals from 2-pyridinecarboxamide were identified in Bacillus samples including Bacillus anthracis, and its origin was traced to the cell wall peptidoglycan macromolecule. 3-Hydroxymyristic acid is a component of lipopolysaccharides in the cell walls of Gram-negative organisms. The Gram-negative Escherichia coli organism showed significant amounts of 3-hydroxymyristic acid derivatives and degradation products in Py-GC-MS analyses. Some of the fatty acid derivatives were observed in very low abundance in the ion mobility spectra, and the higher boiling lipid species were absent. Evidence is presented that the Py-GC-ambient temperature and pressure-IMS system generates and detects bacterial biochemical information that can serve as components of a biological classification scheme directly correlated to the Gram stain reaction in microorganism taxonomy.

Clinical trial experiences with Physioneal™

The kidneys play an important role in maintaining the acid-base balance, as they excrete hydrogen ions and regenerate bicarbonate, thereby regulating intra- as well as extracellular pH, which are vital for normal cell function. In patients with renal failure, the inability of the kidneys to excrete an excess of hydrogen ions results in metabolic acidosis due to retention of acid degradation products, which has a detrimental effect on protein as well as amino acid turnover and leads to hypercatabolism1. In these patients, treatment with bicarbonate has been shown to improve nitrogen balance and decrease both whole body amino acid oxidation and protein degradation2. Metabolic acidosis also negatively affects cardiac, as well as bone, function. Consequently, one of the most important objectives of any dialysis therapy, including peritoneal dialysis (PD), is to correct acidosis. The correction of acidosis in PD is generally more stable than what can be achieved with intermittent hemodialysis3, and this may be one of the most important advantages of PD compared to hemodialysis. Historically, bicarbonate was the first buffer used in PD to correct uremic acidosis. However, the use of this buffer was soon discontinued due to its poor stability in the PD solution4. In a search for alternative buffering agents, bicarbonate was replaced by either lactate or acetate. Both buffers maintain effective acid-base balance as they react with hydrogen ions derived from carbonic acid, thereby regenerating bicarbonate. Acetate, however, was subsequently found to be associated with loss of ultrafiltration and sclerosing peritonitis5. Its use was abandoned in the 1980s, leaving lactate as the only buffer used in PD for many years.

Study of stability of methotrexate in acidic solution Spectrofluorimetric determination of methotrexate in pharmaceutical preparations through acid-catalyzed degradation reaction

Study of the degradation reaction of methotrexate (MTX) in acidic solution was carried out. Optimization of the experimental parameters of MTX acid hydrolysis was investigated. Spectrofluorimetric method for determination of MTX through measurement of its acid-degradation product, 4-amino-4-deoxy-10-methylpteroic acid (AMP), was developed. Stability of the standard solution of MTX prepared in sulfuric acid was discussed in the view of accelerated stability analysis. Two other comparative spectroflourimetric methods based on measuring the fluorescence intensities from either a condensation reaction with acetylacetone–formaldehyde (Hantzsch reaction) or a reaction with fluorescamine were also described. Beer's law validation, accuracy, precision, limits of detection, limits of quantification, and other aspects of analytical merit are presented in the text. The proposed methods were successfully applied for the analysis of MTX in pure drug and tablets dosage form. The sensitivity of the developed methods was favorable, so it was possible to be adopted for determination of MTX in plasma samples for routine use in high-dose MTX therapy.

Chromatographic determination of clotrimazole, ketoconazole and fluconazole in pharmaceutical formulations

High-performance liquid chromatographic technique has been developed for the determination or some azolcsantifungals namely, clotrimazole (CZ), ketoconazole (KZ) and fluconazole (FZ), in pure forms and in pharmaceutical formulations. The proposed HPLC-method can be successfully applied as a stability indicating method for the determination of CZ in presence of its acid degradation products; viz (2-chlorophenyl) -diphenyl methanol and imidazole. The analyzed drugs were separated on a reversed-phase column [Bondapak™ C18 (10 μm, 25 cm×4.6 mm, i.d.)] using a mobile phase containing acetonitrilc+25 mM trishydroxymeihyl aminomethane in phosphate butter (pH 7)=55:45 (v/v), with UV-detection at 260 nm. The differences in the retention times (tR) of the three azoles permit their use as internal standard for each other. In addition, a coupled TLC-densitometric method has been also applied as a stability indicating method to separate and quantify CZ alone or in presence of byproducts impurities and/or its acid degradation products. The TLC-fractionation was performed on a precoatcd silica gel F254 plates using a solvent system consisting of chloroform+acetone+ammonia (25%) (7:1:0.1, by volumes), CZ was well separated from its acid degradation products and quantified by densitometric scanning at 260 nm.

Novel Chromatographic Separation and Carbon Solid-Phase Extraction of Acetanilide Herbicide Degradation Products

One acetamide and 5 acetanilide herbicides are currently registered for use in the United States. Over the past several years, ethanesulfonic acid (ESA) and oxanilic acid (OA) degradation products of these acetanilide/acetamide herbicides have been found in U.S. ground waters and surface waters. Alachlor ESA and other acetanilide degradation products are listed on the U.S. Environmental Protection Agency's (EPA) 1998 Drinking Water Contaminant Candidate List. Consequently, EPA is interested in obtaining national occurrence data for these contaminants in drinking water. EPA currently does not have a method for determining these acetanilide degradation products in drinking water; therefore, a research method is being developed using liquid chromatography/negative ion electrospray/mass spectrometry with solid-phase extraction (SPE). A novel chromatographic separation of the acetochlor/alachlor ESA and OA structural isomers was developed which uses an ammonium acetate-methanol gradient combined with heating the analytical column to 70 degrees C. Twelve acetanilide degradates were extracted by SPE from 100 mL water samples using carbon cartridges with mean recoveries >90% and relative standard deviations < or =16%.