Quantitative Analysis of 26 Opioids, Cocaine, and Their Metabolites in Human Blood by Ultra Performance Liquid Chromatography–Tandem Mass Spectrometry

Abstract

A sensitive and selective ultra performance liquid chromatographic-tandem mass spectrometric method was developed and fully validated for the simultaneous determination of (in order of chromatographic elution) methylecgonine, pholcodine, morphine, hydromorphone, oxymorphone, norcodeine, codeine, dihydrocodeine, oxycodone, 6-Monoacetylmorphine (6-MAM), hydrocodone, ethylmorphine, norfentanyl, benzoylecgonine, tramadol, normeperidine, meperidine, cocaine, pentazocine, cocaethylene, fentanyl, norbuprenorphine, 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, propoxyphene, and methadone in blood. The matrixes analyzed during the validation experiments were as follows: citrated blank plasma for calibrators, fluoride blank plasma for internal quality control (QC), lyophilized serum for external QC, fluoride plasma and whole blood for authentic samples, and lyophilized serum and whole blood for proficiency testing schemes. Samples were extracted with cation exchange solid-phase extraction cartridges. The target drugs were separated and quantified in a chromatographic run of 8.1 minutes using 0.1% formic acid in water and methanol (with 0.1% formic acid) as mobile phase. The limit of quantification ranged from 0.5 to 2.5 ng/mL depending on the compound and the therapeutic concentration. The intra- and interassay precision was less than 15% for all the compounds (except for pentazocine and EDDP, which was <20%) determined with 2 internal and 2 external QC samples, and the bias was within ±15% (except for methylecgonine, which was <20%). Extraction efficiency was greater than 70% for all the compounds except for EDDP. Matrix effects were evaluated with authentic blood samples (n = 10), and they ranged from 47 to 95%, but they were compensated for most analytes using deuterated analogs as internal standards. Prepared samples were stable for 62 hours in the autosampler. This method was successfully applied to authentic samples (n = 120), involving the use of heroin, cocaine, tramadol, and methadone, and to proficiency testing schemes.

Driving Under the Influence of Drugs: A Single Parallel Monitoring-Based Quantification Approach on Whole Blood

“…The determination of such ME is therefore crucial to ensure a proper detection and quantification of the substances of interest. ME ranged from −51% (15% CV) of ion suppression for THC at low concentration and 3% (13% CV) of ion enhancement for lorazepam, being consistent with the existing literature (Table 3) (Simonsen et al, 2010;Fernandez Mdel et al, 2013;Montenarh et al, 2014;Steuer et al, 2014;Vaiano et al, 2016;De Boeck et al, 2017). All values concerning RE and ME are summarized in Table 3.…”

Analysis of drugs of abuse in human plasma by dispersive liquid–liquid microextraction and high‐performance liquid chromatography

“…Precision was determined at three different drug concentration levels in plasma (0.1, 0.5 and 5 μg ml -1 ), and the coefficients of variation were acceptable (Table 2). Napoletano et al (2012) obtained similar results, and other authors (Bassan et al, 2011;Dowling & Regan, 2011;Ramírez Fernández et al, 2013) also using LC-MS/MS for determinations reported higher precision values.…”

Simultaneous quantitation of meperidine, normeperidine, tramadol, propoxyphene and norpropoxyphene in human plasma using solid‐phase extraction and gas chromatography/mass spectrometry: Method validation and application to cardiovascular safety of therapeutic doses

“…Numerous analytical methods have been described for the quantitative determination of MEP, TRAM or dextropropoxyphene, alone or with their metabolites, in plasma samples. Gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) are the main techniques used for most of these methods.…”