ABSTRACT
Understanding the interplay of structural features responsible for molecular assembly is essential for molecular crystal engineering. When assembling molecules with encoded motifs, first choice supramolecular strategies almost always include robust directional nonbonded contacts. Quasiracemic materials, considered near racemates since cocrystallization occurs with chemically unique components, lack a molecular framework or functional group restrictions, highlighting the importance of molecular shape to molecular assembly. Recently, our group reported quasiracemates derived from benzoyl leucine/phenylalanine derivatives with two points of chemical difference. In this study, we modified the chemical framework with valine and increased the scope of the work by imposing a larger variance in the side chain substituents. Pairing a CF3 component with quasienantiomers that differ iteratively from hydrogen to t-butyl offers an important view into the supramolecular landscape of these materials. Single-crystal X-ray crystallography and lattice energy assessments, coupled with conformational and crystal structure similarity searches, show an elevated degree of isomorphism for many of the targeted 17 racemates and quasiracemates. These benzoyl amino acid molecular architectures create extended hydrogen-bond patterns in the crystal that provide enhanced opportunities to study the shape space and molecular recognition profiles for a diverse family of quasienantiomeric components.
ABSTRACT
Purpose: Illicit drug use continues to be a concern for adults on opioid therapy for chronic pain. Prescribers use tools such as urine screening and confirmatory testing with mass spectrometry to monitor adherence to chronic opioid therapy contracts. Design: A cross sectional retrospective study was conducted using electronic medical records. Methods: Data was analyzed from 6558 urine samples of adult outpatients receiving opioid therapy at an urban pain specialty clinic who consented to urine drug tests. Results: From October 18, 2021, to October 21, 2022, 569 were positive amphetamine with immunoassay testing. 310 (54%) of those samples were absent amphetamine with or without methamphetamine while 259 (45.5%) were true positive amphetamine proven by confirmation testing. Analysis of confirmatory testing results identified 281 samples positive for amphetamine with or without methamphetamine. 71 samples confirmed positive for methamphetamine with or without amphetamine. 37 (52.1%) of those methamphetamine samples screened positive for amphetamine and 34 (47.9%) samples screened negative for amphetamine. 48 of the methamphetamine samples were sent for chiral confirmation testing. 45 (93.8%) samples were positive for D-methamphetamine while 3 (6.2%) samples were positive for L-methamphetamine. Only 5 (11.1%) of the 45 patients whose samples were positive for d-methamphetamine reported the use of illicit drugs before their urine sample was tested. Discussion: Confirmatory testing with mass spectrometry can detect illicit drugs, such as methamphetamine, with high sensitivity and specificity and should be used with all samples given the low sensitivity of screening immunoassay. It is of utmost importance that opioid pain medicine prescribers know the many possible interpretations of these results so that they are equipped to make appropriate clinical decisions to ensure the safety of the patient, prescriber, and practice.
