Multilaboratory Collaborative Study of a Nontarget Data Acquisition for Target Analysis (nDATA) Workflow Using Liquid Chromatography-High-Resolution Accurate Mass Spectrometry for Pesticide Screening in Fruits and Vegetables.

Nontarget data acquisition for target analysis (nDATA) workflows using liquid chromatography-high-resolution accurate mass (LC-HRAM) spectrometry, spectral screening software, and a compound database have generated interest because of their potential for screening of pesticides in foods. However, these procedures and particularly the instrument processing software need to be thoroughly evaluated before implementation in routine analysis. In this work, 25 laboratories participated in a collaborative study to evaluate an nDATA workflow on high moisture produce (apple, banana, broccoli, carrot, grape, lettuce, orange, potato, strawberry, and tomato). Samples were extracted in each laboratory by quick, easy, cheap, effective, rugged, and safe (QuEChERS), and data were acquired by ultrahigh-performance liquid chromatography (UHPLC) coupled to a high-resolution quadrupole Orbitrap (QOrbitrap) or quadrupole time-of-flight (QTOF) mass spectrometer operating in full-scan mass spectrometry (MS) data-independent tandem mass spectrometry (LC-FS MS/DIA MS/MS) acquisition mode. The nDATA workflow was evaluated using a restricted compound database with 51 pesticides and vendor processing software. Pesticide identifications were determined by retention time (tR, ±0.5 min relative to the reference retention times used in the compound database) and mass errors (δM) of the precursor (RTP, δM ≤ ±5 ppm) and product ions (RTPI, δM ≤ ±10 ppm). The elution profiles of all 51 pesticides were within ±0.5 min among 24 of the participating laboratories. Successful screening was determined by false positive and false negative rates of <5% in unfortified (pesticide-free) and fortified (10 and 100 µg/kg) produce matrices. Pesticide responses were dependent on the pesticide, matrix, and instrument. The false negative rates were 0.7 and 0.1% at 10 and 100 µg/kg, respectively, and the false positive rate was 1.1% from results of the participating LC-HRAM platforms. Further evaluation was achieved by providing produce samples spiked with pesticides at concentrations blinded to the laboratories. Twenty-two of the 25 laboratories were successful in identifying all fortified pesticides (0-7 pesticides ranging from 5 to 50 µg/kg) for each produce sample (99.7% detection rate). These studies provide convincing evidence that the nDATA comprehensive approach broadens the screening capabilities of pesticide analyses and provide a platform with the potential to be easily extended to a larger number of other chemical residues and contaminants in foods.

Study of the enhancement of dipolar resonant excitation by linear ion trap simulations.

Resolution improvements in dipolar resonant excitation have been examined in a round-rod quadrupolar collision cell for values of the Mathieu characteristic exponent beta equal to n/p, where n and m are small integers (prime beta values) versus other beta values where n and p are not small (ordinary beta values). The trajectories of ions moving in the time-varying electric fields of a quadrupole with and without buffer-gas molecules were calculated to determine the relationship of prime and ordinary beta values to frequency resolution for resonant ion excitation and ejection. For prime beta values, the ion trajectory in the hyperbolic quadrupole field will be exactly periodic with a period of at most 4 pi p/Omega, where Omega is the angular frequency of the main drive radio-frequency (RF) potential. Ion trajectory simulations with prime beta versus ordinary beta values show that the motion of ions with prime beta values have simpler trajectories of shorter periods. Frequency response profiles (FRPs) for round-rod quadrupoles at zero pressure show that dipolar resonant excitations with prime beta values exhibit significantly narrower bandwidths than those with ordinary beta values. Simulations show that at 0.05 to 0.8 mTorr of nitrogen, it is possible to reduce the FRP bandwidth by 20% (measured at 50% depth).

MS(n) characterization of protonated cyclic peptides and metal complexes.

MS(n) experiments involving low energy collisionally activated dissociation (CAD) in a quadrupole ion trap were used to characterize the fragmentation of alkali, alkaline earth and transition metal complexes of five cyclic peptides, and the results were compared with those obtained for protonated cyclic peptides. Complexes with metal ions produced enhanced abundances of the most diagnostic fragments for elucidating the primary structures. For cyclosporin A, nickel and lithium complexes gave additional sequence information compared with the protonated peptide. For depsipeptides, sodium and lead complexes were superior to the protonated peptide or other metal complexes for sequencing residues, and CAD of the lead complexes led to preferential cleavage of two residues at a time. For cyclic lipopeptides, complexes with silver, nickel and strontium ions provided enhanced abundances of key fragment ions.

Evaluation of alkali and alkaline earth metal cation selectivities of lariat ether amides by electrospray ionization mass spectrometry.

Lariat ethers with pendant amide groups have shown promise as new ion sensors because of their selectivity towards particular metal ions. In this study we report alkali and alkaline earth metal binding selectivities of dibenzo-16-crown-5 and fifteen dibenzo-16-crown-5 lariat ether amides (LEAs) as determined by electrospray ionization mass spectrometry (ESI-MS). Additionally, the influence of the acid/base nature of the solution on metal cation selectivity is investigated. The validity of using ESI-MS for determination of selectivities is established by analogous experiments using hosts with known binding constants for the same metal cations and solvent systems. Collisionally activated dissociation (CAD) is used to evaluate the influence of the alkali metal cation binding on the fragmentation of the LEAs.

Complexation of silver and co-recovered metals with novel aza-crown ether macrocycles by electrospray ionization mass spectrometry.

Electrospray ionization mass spectrometry (ESI-MS) is used to evaluate the metal binding selectivities of an array of novel caged macrocycles for silver, gold, copper, nickel, zinc, iron, lead, manganese and alkali metal ions. It is found that five of the new compounds display silver selectivity, and their relative affinities for various metals depend on the type, number, and arrangement of heteroatoms (N, O), the cavity size, and the presence of aromatic substituents. Alkali metal cation binding studies are used to evaluate the size-selectivities of the cavities of the macrocycles. Electronic structure calculation by B3LYP density function theory methods were used to model the metal complexes. The presence of nitrogen atoms in the macrocyclic ring is essential for silver selectivity over other transition metals and alkali metal ions, and the presence of aromatic groups also enhances silver avidity. Macrocycle 3, a triaza-18-crown-6 analog modified with two phenyl groups and a cage group, is capable of selective extraction of Ag+ from aqueous solutions in the presence of other transition metal ions and the most common alkali and alkaline earth metal ions.

Metal complexation of thiacrown ether macrocycles by electrospray ionization mass spectrometry.

In the present study, electrospray ionization mass spectrometry is used to evaluate the metal-binding selectivities of an array of novel caged macrocycles for mercury(II), lead(II), cadmium(II), and zinc(II) ions. In homogeneous methanol/chloroform solutions as well as extractions of metals from aqueous solution by macrocycles in chloroform, it is found that the type of heteroatom (S, O, N), cavity size, and presence of other substituents influence the metal selectivities. Several of the macrocycles in this study bind mercury ion very selectively and efficiently in the presence of many other metal ions and have an avidity toward mercury that was tunable by the size and combination of heteroatoms in the macrocycle ring and the number of cage groups attached. The extraction mechanism was further investigated by determining the variation in extraction selectivity as a function of the counterions of the mercury salts.