This study aims to resolve one of the longest-standing problems in mass spectrometry, which is how to accurately identify an organic substance from its mass spectrum when a spectrum of the suspected substance has not been analyzed contemporaneously on the same instrument. Part one of this two-part report describes how Rice−Ramsperger−Kassel−Marcus (RRKM) theory predicts that many branching ratios in replicate electron−ionization mass spectra will provide approximately linear correlations when analysis conditions change within or between instruments. Here, proof-of-concept general linear modeling is based on the 20 most abundant fragments in a database of 128 training spectra of cocaine collected over 6 months in an operational crime laboratory. The statistical validity of the approach is confirmed through both analysis of variance (ANOVA) of the regression models and assessment of the distributions of the residuals of the models. General linear modeling models typically explain more than 90% of the variance in normalized abundances. When the linear models from the training set are applied to 175 additional known positive cocaine spectra from more than 20 different laboratories, the linear models enabled ion abundances to be predicted with an accuracy of <2% relative to the base peak, even though the measured abundances vary by more than 30%. The same models were also applied to 716 known negative spectra, including the diastereomers of cocaine: allococaine, pseudococaine, and pseudoallococaine, and the residual errors were larger for the known negatives than for known positives. The second part of the manuscript describes how general linear regression modeling can serve as the basis for binary classification and reliable identification of cocaine from its diastereomers and all other known negatives.

Ions stored in an electrodynamic ion trap can be forced from the center of the ion trap to regions of higher radio frequency (RF) electric fields by exposing them to a dipolar DC (DDC) potential applied across opposing electrodes. Such ions absorb power from the trapping RF field, resulting in increased ripple motion at the frequency of the trapping RF. When a bath gas is present, ions undergo energetic collisions that result in “RF-heating” sufficient to induce fragmentation. DDC is therefore a broad-band (i.e., mass-to-charge-independent) means for collisional activation in ion traps with added bath gas. Under appropriate conditions, the internal energy distribution of an ion population undergoing dissociation can be approximated with an effective temperature, Teff. In such cases, it is possible to determine thermal activation parameters, such as Arrhenius activation energies and A-factors, by measuring dissociation kinetics. In this work, the well-studied thermometer ion, protonated leucine enkephalin, was subjected to DDC activation under rapid energy exchange conditions and in two separate bath gases, N2 and Ar, to measure Teff as a function of the ratio of DDC and RF voltages. As a result, an empirically derived calibration was generated to link experimental conditions to Teff. It was also possible to quantitatively evaluate a model described by Tolmachev et al. that can be used to predict Teff. It was found that the model, which was derived under the assumption of an atomic bath gas, accurately predicts Teff when Ar was used as the bath gas but overestimates Teff when N2 was the bath gas. Adjustment of the Tolmachev et al. model for a diatomic gas resulted in an underestimate of Teff. Thus, use of an atomic gas can provide accurate activation parameters, while an empirical correction factor should be used to generate activation parameters using N2.

The laboratory experiment presented here describes the use of a calcium ion-selective electrode (Ca-ISE) to determine the concentration of zinc in a supplement tablet. This approach was developed to show students how to expand the range of applications of Ca-ISE to enable the determination of metal ions other than Ca 2+ . To determine the concentration of Zn 2+ , students dissolved the sample in a Ca-EDTA buffer solution and used EDTA as titrant. We discuss with students the importance of a fixed pH and ionic strength for the accurate analytical quantification. Students also used colorimetric titration of the same sample with murexide as an indicator to determine the concentration of Zn 2+ . They used statistical tools to confirm that the two approaches provide similar results. Students concluded that both titrations overestimate the amount of zinc in a tablet by 3−5% in comparison with the known value reported by the manufacturer and discussed factors that affect the accuracy of Zn 2+ determination.

Nucleophilic substitution covalent modification ion/ion reactions were carried out in a linear quadrupole ion trap between the doubly protonated peptides KGAIL­KGAILR, RAR­ARAA, and RKR­ARAA and isomers of either singly deprotonated 3- or 4-sulfobenzoic acid (n-SBA) esterified with either N-hydroxysuccinimide (NHS) or 1-hydroxy-7-aza-benzotriazole (HOBt). The cation/anion attachment product, through which the covalent reaction occurs, was isolated and subjected to dipolar DC (DDC) activation to generate covalently modified product over the ranges of DDC activation energies and times. The resulting survival yields were used to determine reaction rates, and Tolmachev’s effective ion temperature was used to extract Arrhenius and Eyring activation parameters. It was found that the kinetics determined under these conditions are highly sensitive to the identities and locations of the nucleophilic sites on the peptides, the leaving groups on the reagent, and the location of the attachment sites on the reagent and analyte. Depending upon the identity of the analyte/reagent combination, significant variations in activation energy or entropy (or both) were both found to underlie the measured rate differences. The determination of dissociation kinetics under DDC conditions and application of Tolmachev’s effective ion temperature treatment enables unique insights into the dynamics of gas-phase covalent bond formation via ion/ion reactions.

In both general chemistry and analytical chemistry courses, students are introduced to the concept of predominant species in solution when discussing acid/base chemistry. Speciation diagrams are often used to illustrate the concept and predict the relative abundance of species in solution. Herein, we describe a laboratory experiment for an undergraduate analytical chemistry course, in which students directly measure the speciation diagram and compare it to the diagram calculated using equations they derive in lectures. In this laboratory experiment, students prepare solutions of fixed pH in the pH range 0–14 and use them to measure the speciation diagram of thymol blue with UV–vis spectrophotometry. After collecting the absorbance spectra of all the solutions, students perform a series of data processing steps to derive the speciation diagram of thymol blue from the experimental data and compare it to the calculated diagram. Finally, students use the speciation diagram to corroborate the expected pH ranges, in which the three forms of thymol blue are predominant species. This experiment provides students with a hands-on experience with buffer preparation, enables a straightforward measurement of the speciation of different forms of a diprotic acid, and helps them visualize the concept of predominant species in solution.