A Comparison of the Validity of Gas Chromatography-Mass Spectrometry and Liquid Chromatography-Tandem Mass Spectrometry Analysis of Urine Samples II: Amphetamine, Methamphetamine, ( )-3,4-Methylenedioxyamphetamine, ( )-3,4-Methylenedioxymethamphetamine, ( )-3,4-Methylenedioxyethylamphetamine, Phencyclidine, and ( )-11-nor-9-Carboxy- 9-tetrahydrocannabinol

Abstract

On November 25, 2008, the U.S. Department of Health and Human Services posted a final notice in the Federal Register authorizing the use of liquid chromatography-tandem mass spectrometry (LC-MS-MS) and other technologies in federally regulated workplace drug testing (WPDT) programs. To support this change, it is essential to explicitly demonstrate that LC-MS-MS, as a technology, can produce results at least as valid as gas chromatography (GC)-MS, the long-accepted standard in confirmatory analytical technologies for drugs of abuse. A series of manufactured control urine samples (n = 10 for each analyte) containing amphetamine, methamphetamine, (±)-3,4-methylenedioxyamphetamine, (±)-3,4-methylenedioxymethamphetamine, (±)-3,4-methylenedioxyethylamphetamine, phencyclidine, and (±)-11-nor-9-carboxy-Δ⁹-tetrahydrocannabinol at concentrations ranging from 10% to 2000% of federal cutoffs were analyzed with replication by five federally regulated laboratories using GC-MS and at RTI International using LC-MS-MS. Interference samples as described in the National Laboratory Certification Program 2009 Manual were analyzed by GC-MS and LC-MS-MS as well as previously confirmed urine specimens of WPDT origin. Matrix effects were assessed for LC-MS-MS. Results indicated that LC-MS-MS analysis produced results at least as precise, accurate, and specific as GC-MS for the analytes investigated in this study. Matrix effects, while evident, could be controlled by the use of matrix-matched controls and calibrators with deuterated internal standards.

Ondansetron can enhance cisplatin-induced nephrotoxicity via inhibition of multiple toxin and extrusion proteins (MATEs)

“…However, the Ki values of ondansetron for MATE1 (0.035 μM) and MATE2-K (0.015 μM) were much lower than that for OCT2 (3.85 μM), by 109 and by 256 folds respectively, indicating that ondansetron is a much potent inhibitor for the formers than the latter. The plasma peak concentrations of ondansetron in patients has been reported to range from 0.10 to 0.42 μM from doses of 8 mg to 32 mg daily (Stout et al, 2010). A Ki value of at least more than one-tenth of C max has been suggested for the drug to cause a clinically recognizable interaction with another drug that is transported by the same transporter (Fenner et al, 2009).…”

Improved identification of multiple drugs of abuse and relative metabolites in urine samples using liquid chromatography/triple quadrupole mass spectrometry coupled with a library search

“…analyzed identical samples by using GC/MS and LC/MS/MS and compared the obtained results. LC/MS/MS provided the same accuracy, precision, and specificity in detecting amphetamine (AMP)‐like drugs, morphine (MOR), codeine (COD), 6‐acetylmorphine, and benzoylecgonine as GC/MS did …”

Effect of Ondansetron on Metformin Pharmacokinetics and Response in Healthy Subjects

“…However, ondansetron has a larger inhibitory potency against MATEs as compared with OCTs (Tzvetkov et al, 2012;Li et al, 2013). It has been reported that the peak plasma concentrations of ondansetron in patients range from 0.10 to 0.42 mM from the dose of 8 mg to 32 mg daily (Stout et al, 2010). A K i value of at least more than one-tenth of C max has been considered for the drug to cause a clinically relevant interaction with another drug that is a substrate of the same transporter (Fenner et al, 2009).…”