Identification of Erectile Dysfunction Drugs in Dietary Supplements by Liquid Chromatography Ion Trap Mass Spectrometry.

With the rise in consumption of dietary supplements for various ailments such as erectile dysfunction (ED), there is concern that these supplements may contain illegally added phosphodiesterase type 5 (PDE-5) inhibitor and its analogs. HPLC or LC is a general separation method, and MS is a detection technique, together LC/MS/MS technology provides the mass spectral confirmation in identifying sildenafil, vardenafil, tadalafil and their analogs. In our present study, a sample extraction technique with 1:1 acetonitrile: water solvents and sonication was used for screening, then identification was performed using an LC coupled with Velos Pro linear ion trap mass spectrometry. This was a simple and reliable method for a variety of matrices of dietary supplements and pharmaceutical formulations in tablet, capsule or liquid form. The run time is only 6.5 min, allowing for a quick screening and identification of all of analytes of ED drugs using full scan and data-dependent scan MS/MS, except for tadalafil and aminotadalafil (MS/MS/MS). To conclude this study, Sildenafil, tadalafil, vardenafil, and other 16 analogs in dietary supplements could be quickly screened and identified by HPLC coupled with ion trap MS using data dependent scanning function. The main method using the short column is very rapid, and saves a lot of running time and solvents, and the identification is further confirmed by MS/MS information. The current study develops and validates a quick and reliable method to screen for ED drugs.

Severe Lung Injury Associated With Use of e-Cigarette, or Vaping, Products-California, 2019.

Importance: Since August 2019, more than 2700 patients have been hospitalized with e-cigarette, or vaping, product use-associated lung injury (EVALI) across the United States. This report describes the outbreak in California, a state with one of the highest case counts and with a legal adult-use (recreational) cannabis market. Objective: To present clinical characteristics and vaping product exposures of patients with EVALI in California. Design, Setting, and Participants: Case series describing epidemiologic and laboratory data from 160 hospitalized patients with EVALI reported to the California Department of Public Health by local health departments, who received reports from treating clinicians, from August 7 through November 8, 2019. Exposures: Standardized patient interviews were conducted to assess vaping products used, frequency of use, and method of product acquisition. Vaping products provided by a subset of patients were tested for active ingredients and other substances. Main Outcomes and Measures: Demographic and clinical characteristics, level of care, and outcomes of hospitalization were obtained from medical record review. Results: Among 160 patients with EVALI, 99 (62%) were male, and the median age was 27 years (range, 14-70 years). Of 156 patients with data available, 71 (46%) were admitted to an intensive care unit, and 46 (29%) required mechanical ventilation. Four in-hospital deaths occurred. Of 86 patients interviewed, 71 (83%) reported vaping tetrahydrocannabinol (THC)-containing products, 36 (43%) cannabidiol (CBD)-containing products, and 39 (47%) nicotine-containing products. Sixty-five of 87 (75%) THC-containing products were reported as obtained from informal sources, such as friends, acquaintances, or unlicensed retailers. Of 87 vaping products tested from 24 patients, 49 (56%) contained THC. Vitamin E or vitamin E acetate was found in 41 (84%) of the THC-containing products and no nicotine products. Conclusions and Relevance: Patients' clinical outcomes and vaping behaviors, including predominant use of THC-containing products from informal sources, are similar to those reported by other states, despite California's legal recreational cannabis market. While most THC products tested contained vitamin E or vitamin E acetate, other underlying cause(s) of injury remain possible. The California Department of Public Health recommends that individuals refrain from using any vaping or e-cigarette products, particularly THC-containing products from informal sources, while this investigation is ongoing.

Electrolyte-induced ionization suppression and microcystin toxins: ammonium formate suppresses sodium replacement ions and enhances protiated and ammoniated ions for improved specificity in quantitative LC-MS-MS.

This study examines the effects of electrolytes on microcystin (MC) electrospray ionization (ESI) mass spectrometry and quantitative LC-MS-MS. Sodium replacement ions (SRI) are prominent in MC ESI spectra in protic solvents such as HPLC grade methanol. In a methanol-water-0.006% acetic acid (v/v) gradient, envelopes with up to 11 SRI were apparent in both the +1 and +2 charge states with structures [M + Na(x) - (x-1)H](+) and [M + Na(x) - (x-2)H](+2). The m/z 135 product ion, [Ø-CH(2)-CH=O-CH(3)](+), widely used in tandem LC-MS-MS determination of MC, is a low collision energy fragment of many doubly charged MC precursor ions (e.g., [M+Na+H](+2), [M+Na+NH(4)](+2), M+Na+H+CH(3)OH](+2), [M+2H](+2)). These phenomena impair congener-specific LC-MS-MS detection of MC and degrade quantitative accuracy and precision. Pulse addition experiments established that ammonium formate (AF) strongly suppresses SRI in both +1 and +2 charge states and enhances MH(+) and MNH(4)(+) adducts in neutral MC. Addition of the buffer either post-column or by incorporation in the mobile phase increases specificity for all of the MC which were determined as the MNH(4)(+) > MH(+) and MH(+) > [MH - 134](+) transitions for neutral MC (MCLA, MCLF, MCLW) and [M+2H](+2) > 135(+) and [M+2H](+2) > [M+2H - 135](+) transitions for arginine-containing MC (MCLR, MCYR, MCRR). These findings shed light on mechanisms of electrolyte-induced ionization suppression, and demonstrate beneficial use of a buffer electrolyte for improved specificity and analytical ruggedness in quantitative LC-MS-MS.

An automated method on analysis of blood steroids using liquid chromatography tandem mass spectrometry: application to population screening for congenital adrenal hyperplasia in newborns.

BACKGROUND: Newborn screening for congenital adrenal hyperplasia (CAH) is commonly accomplished by measurement of 17-α-hydroxyprogestrone (17-OHP) using enzyme immunoassay (EIA). EIA contributes a significant number of false positives. Therefore, second-tier steroid profile by liquid chromatography-tandem mass spectrometry (LC-MS/MS) is warranted. METHODS: Dried blood spots (DBS) were extracted with a mixture of methanol and water containing the deuterium labeled internal standards of d(8)-17-OHP, d(7)-androstenedione, and d(4)-cortisol. The final extracts were analyzed for 17-OHP, androstenedione and cortisol by LC-MS/MS in the multiple reaction monitoring (MRM) mode. RESULTS: Mean recoveries of the target analytes, 17-OHP, androstenedione and cortisol, were between 97 and 115% with an average intra- and inter-assay CVs ranging from 3.9-9.9% to 3.6-10.1%, respectively. The high efficiency of this method enabled us to test 11,598 specimens, identified as indeterminate by EIA in ~6 years; resulting in 809 presumptive positives reducing the false positives rate by 93%. CONCLUSIONS: The three steroid profile provided better screening outcomes of CAH than 17-OHP concentration alone. Our sample preparation allowed high throughput using common laboratory chemicals. Using three internal standards significantly improved method precision and accuracy. The reduction in false positives significantly reduces anxiety for newborns and their families.

Photodissociation dynamics of CBr4 at 267 nm by means of ion velocity imaging.

The photodissociation dynamics of CBr4 at 267 nm has been studied using time of flight (TOF) mass spectrometry and ion velocity imaging techniques. The photochemical products are detected with resonance enhanced multiphoton ionization (REMPI) as well as single-photon vacuum ultraviolet ionization at 118 nm. REMPI at 266.65 and 266.71 nm was used to detect the ground Br(2P32) and spin-orbit excited Br(2P12) atoms, respectively. The translational energy and angular distributions are consistent with direct dissociation from an excited triplet state and indirect dissociation from high vibrational levels on the singlet ground state surface. Br2+ ions are also observed in the TOF spectra with a focused 267 nm laser. The counter fragment, CBr2+, is observed when this photolysis laser is unfocused, and photons at 118 nm are used to ionize the radical products. The translational energy distributions of the CBr2+ and Br2+ products can be momentum matched, which indicates that molecular Br2 elimination is one of the primary dissociation channels.

Single-photon spectroscopy of singlet sulfur atoms and the autoionization lifetime measurements of the superexcited singlet states.

Single-photon excitation spectra from the lowest singlet (1)D(2) level of sulfur atoms were recorded with a tunable vacuum ultraviolet (VUV) radiation source generated by frequency tripling in noble gases. The photolysis of CS(2) at 193 nm was used to produce the singlet S((1)D(2)) sulfur atoms that were then excited to neutral superexcited states with the tunable VUV radiation. These superexcited states undergo autoionization into the first ionization continuum state of S(+)((4)S(3/2) (o))+e(-), which is not directly accessible from the S((1)D(2)) state via an allowed transition. The excitation spectra were recorded by monitoring the S(+) signal in a velocity imaging apparatus while scanning the VUV excitation wavelength. Three new lines were observed in the spectra which have not been previously reported. The full widths at half maximum (FWHM) of each of the observed transitions were determined by fitting the profiles of each absorption resonances with the Fano formula. Autoionization lifetimes tau of these singlet superexcited states were obtained from FWHM using the Uncertainty Principle. Abnormal autoionization lifetimes were found for the 3s(2)3p(3)((2)D(o))nd((1)D(2)) and the 3s(2)3p(3)((2)D(o))ns((1)D(2)) Rydberg series, in which tau(5d) and tau(7s) are shorter than tau(4d) and tau(6s), respectively. This is contrary to the well-known scaling law of tau(n*) proportional, variantn(*3), which should be followed within a series unless there exist perturbations from other series or new channels open up to which some members of the series can decay. Possible perturbations from the nearby triplet series are suspected for causing the broadening of the 5d and 7s levels.

Reinvestigation of CS2 dissociation at 193 nm by means of product state-selective vacuum ultraviolet laser ionization and velocity imaging.

A branching ratio of 1.6 +/- 0.3 for S(3P)/S(1D) is obtained for the dissociation of CS2 with very low fluence 193 nm laser (less than 2 mJ/cm2), in which the S(3P) and S(1D) have been state-selectively ionized using VUV lasers at different wavelengths. The anisotropy parameters betamax(3P) = 0.8 and betamax(1D) = 1.9 indicate that these channels are preferentially populated at different geometries and the lifetime is very short.

Photodissociation studies of CBr(4) (+) and CBr(3) (+) at 267 nm using ion velocity imaging.

Time-of-flight (TOF) mass spectroscopy and ion velocity imaging were employed to study the formation and photodissociation of CBr(4) (+) and CBr(3) (+) ions that were observed in the TOF spectrum when a CBr(4) beam was irradiated with 118 nm and 355 nm lasers. Energy dependence measurements show that both CBr(4) (+) and CBr(3) (+) ions depend on the fourth power of the 355 nm laser energy, which indicates that direct ionization and dissociative ionization of CBr(4) have low probabilities from the state initially excited at 118 nm. This is likely due to the large geometry change in the CBr(4) (+) ion. Two ionic fragments Br(+) and CBr(2) (+) were observed from the dissociation of CBr(4) (+) and CBr(3) (+) ions when another laser at 267 nm was introduced to the interaction region at a delayed time. The possible dissociation pathways and the angular and translational distributions are discussed in the paper.