Evidence of free radical generation from the interaction of polyethylene glycol with PVC medical tubing.

The combination of polyethylene glycol (PEG) and polyvinyl chloride (PVC) medical tubing was previously demonstrated to degrade an active pharmaceutical ingredient (API), a phenomenon proposed to occur by free radical mechanisms. This study tests the hypothesis that dehydrochlorinated PVC at the tubing surface increases the oxidative potential of PEG autooxidation via radical propagation. The functional group composition at the surfaces of intact, autoclaved, or force-degraded medical grade PVC tubings was assessed by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). The content of double bonds in PVC was correlated with the extent of API degradation in the PEG-PVC system, with the repeated autoclaving cycle treatments yielding the most reactive tubing. After PEG exposure, new functional groups on the surface of PVC were observed, indicating the participation of PVC in the oxidation reactions. The PEG-PVC system was further probed by the fluorinated spin-trap reagent FDMPO, where trapped adducts were analyzed by 19F NMR, revealing the presence of three radical species. Trapped adducts were then analyzed by two-dimensional liquid chromatography tandem mass spectrometry (2D-LC-MS/MS), which revealed the presence of free chlorine atoms and/or hypochlorous acid and a PEG alkoxy radical. Chemical mechanisms describing the interaction between dehydrochlorinated PVC and PEG are proposed to explain the presence of free radicals and the functional group changes in the PVC surface.

Compatibility study of a parenteral microdose polyethylene glycol formulation in medical devices and identification of degradation impurity by 2D-LC/MS.

Polyethylene glycol (PEG) based formulation and polyvinylchloride (PVC) tubing are frequently used for drug delivery and administration. The compatibility of a parenteral drug microdose formulation in intravenous infusion (IV) devices was studied to support the clinical determination of absolute bioavailability by the microdosing method. The investigational microdose formulation containing PEG was found prone to significant loss of potency within hours of storage in the PVC IV tubing due to degradation. Degradation occurred only when both PEG and PVC tubing were present. The degradation product could not be detected by LC/MS due to the significant interference from the high concentration of PEG (4%) matrix and the extremely low level of drug (0.6ppm). To obtain structural information of the degradation impurity and understand the cause of the degradation, a simple heart-cutting 2D-LC/MS approach was utilized to effectively separate the impurity from the complex PEG oligomers and overcome the matrix interference, enabling mass spectrometric analysis of the impurity. An oxidation- dominated mechanism was proposed in which the combination of PEG auto-oxidation and dehydrochlorination of the PVC tubing yielded an oxidative environment that enhanced radical propagation and accelerated degradation of the investigational parent drug.

Products and Mechanism of the Reaction of 1-Pentadecene with NO3 Radicals and the Effect of a -ONO2 Group on Alkoxy Radical Decomposition.

The linear C15 alkene, 1-pentadecene, was reacted with NO3 radicals in a Teflon environmental chamber and yields of secondary organic aerosol (SOA) and particulate ß-hydroxynitrates, ß-carbonylnitrates, and organic peroxides (ß-nitrooxyhydroperoxides + dinitrooxyperoxides) were quantified using a variety of methods. Reaction occurs almost solely by addition of NO3 to the C═C double bond and measured yields of ß-hydroxynitrate isomers indicate that 92% of addition occurs at the terminal carbon. Molar yields of reaction products determined from measurements, a proposed reaction mechanism, and mass-balance considerations were 0.065 for ß-hydroxynitrates (0.060 and 0.005 for 1-nitrooxy-2-hydroxypentadecane and 1-hydroxy-2-nitrooxypentadecane isomers), 0.102 for ß-carbonylnitrates, 0.017 for organic peroxides, 0.232 for ß-nitrooxyalkoxy radical isomerization products, and 0.584 for tetradecanal and formaldehyde, the volatile C14 and C1 products of ß-nitrooxyalkoxy radical decomposition. Branching ratios for decomposition and isomerization of ß-nitrooxyalkoxy radicals were 0.716 and 0.284 and should be similar for other linear 1-alkenes ≥ C6 whose alkyl chains are long enough to allow for isomerization to occur. These branching ratios have not been measured previously, and they differ significantly from those estimated using structure-activity relationships, which predict >99% isomerization. It appears that the presence of a -ONO2 group adjacent to an alkoxy radical site greatly enhances the rate of decomposition relative to isomerization, which is otherwise negligible, and that the effect is similar to that of a -OH group. The results provide insight into the effects of molecular structure on mechanisms of oxidation of volatile organic compounds and should be useful for improving structure-activity relationships that are widely used to predict the fate of these compounds in the atmosphere and for modeling SOA formation and aging.

Influence of functional groups on organic aerosol cloud condensation nucleus activity.

Organic aerosols in the atmosphere are composed of a wide variety of species, reflecting the multitude of sources and growth processes of these particles. Especially challenging is predicting how these particles act as cloud condensation nuclei (CCN). Previous studies have characterized the CCN efficiency for organic compounds in terms of a hygroscopicity parameter, κ. Here we extend these studies by systematically testing the influence of the number and location of molecular functional groups on the hygroscopicity of organic aerosols. Organic compounds synthesized via gas-phase and liquid-phase reactions were characterized by high-performance liquid chromatography coupled with scanning flow CCN analysis and thermal desorption particle beam mass spectrometry. These experiments quantified changes in κ with the addition of one or more functional groups to otherwise similar molecules. The increase in κ per group decreased in the following order: hydroxyl ≫ carboxyl > hydroperoxide > nitrate ≫ methylene (where nitrate and methylene produced negative effects, and hydroperoxide and nitrate groups produced the smallest absolute effects). Our results contribute to a mechanistic understanding of chemical aging and will help guide input and parametrization choices in models relying on simplified treatments such as the atomic oxygen:carbon ratio to predict the evolution of organic aerosol hygroscopicity.

Identification and yields of 1,4-hydroxynitrates formed from the reactions of C8-C16 n-alkanes with OH radicals in the presence of NO(x).

A series of C8-C16 n-alkanes were reacted with OH radicals in the presence of NOx in an environmental chamber and particulate 1,4-hydroxynitrate reaction products were collected by filtration, extracted, and analyzed by high-performance liquid chromatography with UV absorption and electron ionization mass spectrometry (HPLC/UV/MS). Observed mass spectral patterns can be explained by using proposed ion fragmentation mechanisms, permitting the identification of each hydroxynitrate isomer. Reversed-phase retention of these compounds was dictated by the length of the longer of two alkyl chains attached to the 1,4-hydroxynitrate subunit. 1,4-Hydroxynitrates were quantified in particles using an authentic analytical standard for calibration, and the results were combined with gas chromatography measurements of the n-alkanes to determine the molar yields. Yields based on analyses of particles increased with increasing carbon number from 0.00 for C8 to an average plateau value of 0.130 ± 0.008 for C14-C16, due primarily to corresponding increases in gas-to-particle partitioning. The value at the plateau, where essentially all 1,4-hydroxynitrates were in particles, was equal to the average total yield of C14-C16 1,4-hydroxynitrates. The average branching ratio for the formation of C14-C16 1,4-hydroxynitrates from the reaction of NO with the corresponding 1,4-hydroxyperoxy radicals was 0.184 ± 0.011. This value is ∼20% higher than the plateau value of 0.15 for reactions of secondary 1,2-hydroxyperoxy radicals and ∼40% lower than the plateau value of 0.29 for reactions of secondary alkyl peroxy radicals, both of which were reported previously. The branching ratios determined here were used with values reported previously to calculate the yields of C7-C18 alkyl nitrates, 1,4-hydroxynitrates, and 1,4-hydroxycarbonyls, the three products formed from the reactions of these n-alkanes.

Alkyl nitrate formation from the reactions of C8-C14 n-alkanes with OH radicals in the presence of NO(x): measured yields with essential corrections for gas-wall partitioning.

In this study, C8-C14 n-alkanes were reacted with OH radicals in the presence of NO(x) in a Teflon film environmental chamber and isomer-specific yields of alkyl nitrates were determined using gas chromatography. Because results indicated significant losses of alkyl nitrates to chamber walls, gas-wall partitioning was investigated by monitoring the concentrations of a suite of synthesized alkyl nitrates added to the chamber. Gas-to-wall partitioning increased with increasing carbon number and with proximity of the nitrooxy group to the terminal carbon, with losses as high as 86%. The results were used to develop a structure-activity model to predict the effects of carbon number and isomer structure on gas-wall partitioning, which was used to correct the measured yields of alkyl nitrate isomers formed in chamber reactions. The resulting branching ratios for formation of secondary alkyl nitrates were similar for all isomers of a particular carbon number, and average values, which were almost identical to alkyl nitrate yields, were 0.219, 0.206, 0.254, 0.291, and 0.315 for reactions of n-octane, n-decane, n-dodecane, n-tridecane, and n-tetradecane, respectively. The increase in average branching ratios and alkyl nitrate yields with increasing carbon number to a plateau value of ∼0.30 at about C13-C14 is consistent with predictions of a previously developed model, indicating that the model is valid for alkane carbon numbers ≥C3.

Rapid peptide fragmentation without electrons, collisions, infrared radiation, or native chromophores.

Ultraviolet photodissociation of peptides followed by mass analysis has several desirable advantages relative to other methods, yet it has not found widespread use due to several limitations. One shortcoming is the inefficiency with which peptides absorb in the ultraviolet. This issue has a simple solution and can be circumvented by the attachment of noncovalent adducts that contain appropriate chromophores. Subsequent photoactivation of the chromophore leads to vibrational excitation of the complex and eventually to fragmentation of the peptide. Herein, the energetics that control the efficiency of this process are examined as a function of the characteristics of both the peptide and the noncovalently attached chromophore. Fragmentation efficiency decreases with increasing peptide size and is also constrained by the binding energy of the noncovalent adduct. The optimum chromophore should have excellent absorption at the excitation wavelength and a low luminescence quantum yield. It is demonstrated that a naphthyl based 18-crown-6 adduct is ideally suited for attaching to a variety peptides and fragmenting them following absorption of 266 nm light. Potential applications and limitations of this methodology are discussed.