Simultaneous UPLC-MS/MS assay for the detection of the traditional antipsychotics haloperidol, fluphenazine, perphenazine, and thiothixene in serum and plasma.

Background: Most antipsychotic drugs that are commonly prescribed in the USA are monitored by liquid and gas chromatographic methods. Method performance has been improved using ultra high pressure liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). A rapid and simple procedure for monitoring haloperidol, thiothixene, fluphenazine, and perphenazine is described here.

Quantitation of nicotine, its metabolites, and other related alkaloids in urine, serum, and plasma using LC-MS-MS.

We describe a method for the quantitative analysis of nicotine, cotinine, trans-3'-hydroxy cotinine, nornicotine, and anabasine in urine, serum, and plasma using liquid chromatography-tandem mass spectrometry. A mix of deuterium-labeled internal standards (IS) is added to a specimen aliquot. The aliquot is extracted using mixed-mode solid phase extraction and eluted into an autosampler vial for injection into an LC-MS-MS system.

Confirmation of cannabinoids in meconium using two-dimensional gas chromatography with mass spectrometry detection.

Meconium has become the specimen of choice for determining fetal exposure to drugs of abuse, but its physical complexity can cause interferences from matrix effects. A new method to determine 9-carboxy-11-nor-Delta(9)-THC (9-THCA) and 11-hydroxy-Delta(9)-THC (11-OH-THC) using two-dimensional (2D) GC-MS was developed to reduce interferences and carryover. The method was validated using 70 spiked samples prepared in drug-free meconium and 46 residual patient specimens that were confirmed to contain cannabinoids.

Simultaneous determination of codeine, morphine, hydrocodone, hydromorphone, oxycodone, and 6-acetylmorphine in urine, serum, plasma, whole blood, and meconium by LC-MS-MS.

A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for simultaneous analysis of six major opiates in urine, serum, plasma, whole blood, and meconium is described. The six opiates included are codeine, morphine, hydrocodone, hydromorphone, oxycodone, and 6-acetylmorphine (6-AM). The method was compared to an in-house gas chromatography (GC)-MS method and an LC-MS-MS method performed by another laboratory.

Drug monitoring and toxicology: a procedure for the monitoring of levetiracetam and zonisamide by HPLC-UV.

This article describes a rapid isocratic high-performance liquid chromatographic (HPLC) method for the simultaneous measurement of the anticonvulsants levetiracetam and zonisamide. Monitoring these drugs is important for detecting potentially toxic concentrations, particularly in patients with renal impairment, but no commercial assays are currently available. Following a liquid-liquid extraction, levetiracetam (5-150 microg/mL) and zonisamide (5-80 microg/mL) are quantitated by HPLC-UV.

Drug monitoring and toxicology: a procedure for the monitoring of oxcarbazepine metabolite by HPLC-UV.

This article describes a rapid high-performance liquid chromatographic (HPLC) method for the measurement of the primary metabolite of oxcarbazepine. Following a simple precipitation step, 10,11,-dihydro-10-hydroxy-5H-dibenzo(b,f)azepine-5-carboxamide is quantitated (5-60 microg/mL) by analysis on an HPLC-UV system. The instrument time is less than 5 min per injection, an improvement over most published methods.

Simultaneous analysis of the Delta9-THC metabolites 11-nor-9-carboxy-Delta9-THC and 11-hydroxy-Delta9-THC in meconium by GC-MS.

Neonates that are exposed to cannabinoids in utero may have characteristic physical and mental developmental problems throughout their lives. The early identification of exposed neonates allows early intervention and anticipation of potential problems. Testing meconium detects maternal marijuana use over the last four months of gestation, providing a better drug exposure marker than urine.

Assessing analytical specificity in quantitative analysis using tandem mass spectrometry.

Objectives: The necessity of confirmation of compound identity in quantitative analysis is well recognized for methods utilizing single mass spectrometry detection but is not commonly addressed for applications utilizing multiple-stage mass spectrometry (MSn). For MSn detection, no commonly accepted rules for assessment of analytical specificity in quantitative analyses have been established to date.

Methods: To assure compound identity, we evaluated approaches based on monitoring multiple mass transitions of a target compound followed by comparison of the branching ratios of the mass transitions.

Comparison of sample preservation methods for clinical trace element analysis by inductively coupled plasma mass spectrometry.

The effects of chemical additives and storage temperatures on measurement of 16 trace elements in urine by inductively coupled plasma mass spectrometry (ICP-MS) were evaluated. A 24-hour urine specimen was supplemented with concentrations of the elements. Aliquots containing 1 of 4 chemical additives were stored at 3 different temperatures in sealed polypropylene containers.

A rapid procedure for the monitoring of amiodarone and N-desethylamiodarone by HPLC-UV detection.

This article describes a rapid isocratic high-performance liquid chromatographic (HPLC) method for the simultaneous measurement of the antiarrhythmic drug amiodarone and its potentially active metabolite N-desethylamiodarone (DEA). Following a simple liquid-liquid extraction, amiodarone and its metabolite are quantitated (0.3-6.

Analysis of catecholamines in urine by positive-ion electrospray tandem mass spectrometry.

Background: Determination of urinary catecholamines (CATs) is considered important for clinical diagnosis of pheochromocytoma, paraganglioma, and neuroblastoma. The major disadvantages of existing tests include relatively long instrumental analysis time and potential interference from drugs and drug metabolites that are structurally similar to CATs.

Methods: CATs were extracted from a 300-microL aliquot of urine by a two-step liquid-liquid extraction method specific for compounds containing a catechol group.

Analysis of dicarboxylic acids by tandem mass spectrometry. High-throughput quantitative measurement of methylmalonic acid in serum, plasma, and urine.

Background: Methylmalonic acid (MMA) is a dicarboxylic acid whose concentration can be increased in blood and urine in patients with an inborn error of metabolism or vitamin B(12) deficiency. We developed a method for the selective analysis of dicarboxylic acids that exploits the high specificity of tandem mass spectrometry (MS/MS) and the substantial difference in fragmentation patterns of the isomers methylmalonic (MMA) and succinic acid (SA).

Methods: Dicarboxylic acids were extracted from samples with methyl-tert-butyl ether and derivatized with butanolic HCl to form dibutyl esters.

Use of a statistically designed experimental approach to optimize the propylketal derivatization of barbiturates.

The derivatization of barbiturates with dimethylformamide dipropylacetal and dimethylformamide diisopropylacetal is studied with respect to the optimization of reaction recovery and reliability. A second-order orthogonal experimental design is utilized in order to obtain regression equations for the reaction recovery dependence on the derivatization solution composition, incubation temperature, and time for amobarbital, butalbital, pentobarbital, phenobarbital, and secobarbital. Regression equations for the effect of incubation temperature and time on the derivative recovery and the optimum conditions for derivatization recoveries are obtained.

Solid-phase extraction of 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid from urine drug-testing specimens with the cerex polycrom-THC column.

Confirmation of drugs of abuse by gas chromatography-mass spectrometry (GC-MS) is the most time-consuming process used by drug-testing laboratories. Cost effectiveness and competitive turnaround times for testing results demand fast, efficient, and reliable extraction methods. We applied the Cerex Polycrom-THC solid-phase extraction (SPE) column to the extraction of 11-nor-delta9-tetrahydrocannabinol carboxylic acid (9-THCA) from urine.

Comparison of four derivatizing reagents for 6-acetylmorphine GC-MS analysis.

The propionyl, trimethylsilyl, trifluroacetyl, and heptafluoroacyl derivatives of 6-acetylmorphine (6-AM) were evaluated with respect to optimal method performance, derivative stability, and methods characterization for use in gas chromatographic-mass spectrometric (GC-MS) analysis with electron ionization mode and selected ion monitoring. The most common potential interferences and compatibility with other derivatives when used on the same GC-MS were determined for the derivatizing reagents. The propionyl, trimethylsilyl, and trifluroacetyl derivatives produced adequate stability, accuracy, and precision for the method.

Analysis of gabapentin in serum and plasma by solid-phase extraction and gas chromatography-mass spectrometry for therapeutic drug monitoring.

A simple method for the determination of gabapentin (Neurontin) is described. The method uses solid-phase extraction by disk column and derivatization followed by gas chromatographic-mass spectrometric analysis. The single-step derivatization with MTBSTFA produces a t-BDMS derivative of both the carboxylic and amine moieties of the molecule.

Nitrite adulteration of workplace urine drug-testing specimens. I. Sources and associated concentrations of nitrite in urine and distinction between natural sources and adulteration.

The active ingredient in the commercial workplace urine drug-testing adulterant, Klear, was previously determined to be nitrite ion. Nitrite adulteration compromises the confirmation of some drugs, notably the marijuana metabolite. A previously reported bisulfite step overcomes some nitrite adulteration, but it cannot do so in every case, which leaves the laboratory to report the specimen as not suitable for testing.

A positive cannabinoids workplace drug test following the ingestion of commercially available hemp seed oil.

A commercially available health food product of cold-pressed hemp seed oil ingested by one volunteer twice a day for 4 1/2 days (135 mL total). Urine specimens collected from the volunteer were subjected to standard workplace urine drug testing procedures, and the following concentrations of 11-nor-delta9- tetrahydrocannabinol carboxylic acid (9-THCA) were detected: 41 ng/mL 9-THCA at 45 h, 49 ng/mL at 69 h, and 55 ng/mL at 93 h. Ingestion was discontinued after 93 h, and the following concentrations were detected: 68 ng/mL at 108 h, 57 ng/mL at 117 h, 31 ng/mL at 126 h, and 20 ng/mL at 142 h.

Improving ion mass ratio performance at low concentrations in methamphetamine GC-MS assay through internal standard selection.

In federally regulated drug testing, laboratories must identify and quantitate drugs and their breakdown products by gas chromatography-mass spectrometry (GC-MS) to a concentration that is at least 60% below the cutoff concentration for reconfirmation purposes. Use of methamphetamine-d5 as an internal standard in routine testing with derivatization by HFBA was found to contribute m/z 91 and 118 ions to the same ions from the nondeuterated methamphetamine in the specimen. This resulted in poor chromatography and occasionally caused the 91/254 and 118/254 ion mass ratios to exceed the +20% acceptance limit established in the calibration process at low concentrations.

A rapid gas chromatographic method quantitating clozapine in human plasma or serum for the purpose of therapeutic monitoring.

A gas chromatographic method using nitrogen-phosphorus detection was developed to quantitate clozapine in plasma or serum. Methyl clonazepam was used as an internal standard. Sample preparation included a single-step extraction with ethyl acetate, which was injected directly onto a wide-bore capillary column.

A high-performance liquid chromatographic method for quantitating bupropion in human plasma or serum.

We report a high-performance liquid chromatographic (HPLC) procedure for quantitating bupropion in serum or plasma for the purpose of therapeutic monitoring. Bupropion and its internal standard, a fluorinated analogue of bupropion, are extracted into hexane-isoamyl alcohol (96:4) after the addition of 400 microL 0.1N KOH.

The reliability of a solid-phase extraction system for the analysis of benzoylecgonine in urine.

Gas chromatographic-mass spectrometric (GC-MS) analysis for benzoylecgonine (BE), a metabolite of cocaine, requires an initial extraction from urine. Although liquid-liquid extraction methods are frequently used, solid-phase extraction (SPE) may be preferable for obtaining reliable results and clean chromatograms. We describe a 12-month study that evaluates the accuracy, precision, variability between analysts, variability between column lots, and cleanliness of BE extracts using SPE columns followed by GC-MS analysis.

Application of the Technicon Chem 1+ chemistry analyzer to the Syva Emit ethyl alcohol assay in plasma and urine.

The performance of the Technicon Chem 1+ chemistry analyzer with the Syva Emit ethyl alcohol assay in plasma and urine was evaluated. Spiked specimens from 0 to 600 mg/dL were tested, and expected versus measured concentrations were monitored. Linear regression line equations of y = 0.