Identification of Drugs in Parenteral Pharmaceutical Preparations from a Quality Assurance and a Diversion Program by Direct Analysis in Real-Time AccuTOF^TM-Mass Spectrometry (DART-MS)

Abstract

In healthcare settings drug diversion and impairment of physicians are major concerns requiring a rapid and efficient method for surveillance and detection. A Direct Analysis in Real Time ion source coupled to a JEOL AccuTOF TM time-of-flight mass spectrometer (DART-MS) method was developed to screen parenteral pharmaceutical formulations for potential drug diversion. Parenteral pharmaceutical formulations are also known as injectable formulations and are used with intravenous, subcutaneous, intramuscular and intra-articular administration. A library was created using the mass spectra data collected by a DART-MS operated in switching mode at 20, 60 and 90 V settings. This library contained 17 commonly encountered drugs in parenteral pharmaceutical formulations that included the surgical analgesic: fentanyl, hydromorphone and morphine; anesthetic: baclofen, bupivacaine, ketamine, midazolam, ropivacaine and succinylcholine; and a mixture of other drug classes: caffeine, clonidine, dexamethasone, ephedrine, heparin, methadone, oxytocin and phenylephrine. Randomly selected 200 de-identified parenteral pharmaceutical formulations containing one or more drugs were submitted for analysis to the FIRM Toxicology Laboratory at Virginia Commonwealth University Health and were screened using the DART-MS. The drug contents of the de-identified formulations were previously confirmed by a published high performance liquid chromatography (HPLC) method. The drugs in the formulations were rapidly and successfully identified using the generated library. The DART-MS and HPLC results were in complete agreement for all 200 parenteral pharmaceutical formulations.

Diversion of Controlled Drugs in Hospitals: A Scoping Review of Contributors and Safeguards

“…51,79 Implement a drug testing program Drug testing of HCWs has been used in three capacities: pre-employment screening, random testing on an ongoing basis, and when there is reason to suspect impairment (ie, "for cause" drug testing). 18,20,27,60,[80][81][82][83][84][85][86][87][88][89] Some authors caution against random drug testing. 86,87,90 Drug testing is connected with issues of legal discovery and confidentiality, which vary according to local and federal regulations; review the provided references and refer to local statutes and counsel.…”

Interpol review of controlled substances 2016–2019

“…2016 Investigation of a mixture containing Alprazolam, Codeine and Paracetamol using TLC and HPLC [ 1269 ]; Chiral separations of cathinone and amphetamine-derivatives: comparative study between CEC, supercritical fluid chromatography and three liquid chromatographic modes [ 1270 ]; detected cutting agents and the analytical methodology implemented by forensic laboratories (focused on cocaine and heroin) [ 1271 ]; chemiluminescence for simultaneous determination of paracetamol and codeine in pharmaceuticals [ 1272 ]; simultaneous determination of ascorbic acid, acetaminophen and codeine based on multi-walled carbon nanotubes modified with magnetic nanoparticles paste electrode [ 1273 ]; Profiling of 8 years of seizures in Switzerland (5875 cocaine specimens and 2728 heroin specimens) [ 1274 ]; SPME GC-MS method validated for 15 residual solvents in seized cocaine and heroin [ 1275 ]; GC-MS method for the detection and quantification of cathine, cathinone, methcathinone and ephedrine [ 1276 ]; Identification of 17 commonly encountered drugs (fentanyl, hydromorphone and morphine; anesthetic: baclofen, bupivacaine, ketamine, midazolam, ropivacaine and succinylcholine; and a mixture of other drug classes: caffeine, clonidine, dexamethasone, ephedrine, heparin, methadone, oxytocin and phenylephriner) in parenteral pharmaceutical preparations from a quality assurance and a diversion program by AccuTOF(TM)- DART-MS [ 1277 ]; LC-MS-MS method for the simultaneous determination of morphine, codeine, tuberostemonine, thebaine, papaverine, scopoletin, liquiritin, narcotine, gynaroside, hyperoside, hesperidin, isoliquiritin, liquiritigenin, luteolin, isoliquiritigenin, apigenin, formononetin and glycyrrhizic acid in traditional Chinese antitussive medication [ 1278 ]; colorimetric assay for the sensitive and visual detection of morphine and codeine using melamine modified gold nanoparticles (MA-AuNPs) [ 1279 ]; screen-printed electrodes for quantification of cocaine and Delta(9)-THC: adaptions to portable systems for forensic purposes [ 1280 ]; identification of unknown NBOMe drugs (25H–NBOMe, 25D-NBOMe, and 25E-NBOMe) three other phenethylamine-type drugs (25I-NBMD, RH34, and escaline), eight cathinone derivatives (5-DBFPV, 3,4-MDPHP, 3,4-dimethyl-NEB, 3,4-dimethyl-alpha-ethylaminopentiophenone, 3,4-dimethyl-alpha-PVP, 4F-alpha-ethylaminopentiophenone, bk-IVP, and bk-IBP), and a phencyclidine derivative (MMXE) as well as known compounds, 25I–NBOMe, ADB-CHIMINACA, 5F-ADB, and butane-1,4-diol analyzed by GC-MS, HRMS, and NMR [ 1281 ];…”

“…2016 JEOL DART-AccuTOF - MS method was developed to screen parenteral pharmaceutical formulations [ 1277 ]; 2017 a review of pharmacognosy through the centuries including identification, quality and purity [ 1534 ]; series of benzimidazole-piperidine derivatives were synthesized and structures of the compounds were elucidated by FT-IR, H-1 NMR, C-13 NMR, and HRMS spectral data [ 1535 ];…”

Application of Mass Spectroscopy in Pharmaceutical and Biomedical Analysis

“…A library of compounds were analyzed using mass spectra data collected by DART-MS operated in switching mode at 20, 60 and 90 V settings. This library consisted of 17 commonly encountered drugs in parenteral pharmaceutical formulations, that is, surgical analgesic: fentanyl, hydromorphone and morphine; anesthetic: baclofen, bupivacaine, ketamine, midazolam, ropivacaine and succinylcholine; and a mixture of other drug classes: caffeine, clonidine, dexamethasone, ephedrine, heparin, methadone, oxytocin and phenylephrine [37].…”