Drug concentrations in post-mortem specimens.

A meta-analysis of drug concentrations in post-mortem specimens is presented. The analysis involved 50 commonly used drugs and their concentrations in femoral blood, other blood (such as cardiac blood), vitreous humor, muscle, liver, kidney, brain, heart, lung, spleen, and bile. A total of 10 993 analytical results from 5375 post-mortem cases in 388 studies were gathered and the ratios of drug concentrations in tissue material to median femoral blood concentrations were calculated.

Summary statistics for drug concentrations in post-mortem femoral blood representing all causes of death.

Concentration distributions for 183 drugs and metabolites frequently found in post-mortem (PM) femoral venous blood were statistically characterized based on an extensive database of 122 234 autopsy cases investigated during an 18-year period in a centralized laboratory. The cases represented all causes of death, with fatal drug poisonings accounting for 8%. The proportion of males was 74% with a median age of 58 years compared with 26% females with a median age of 64 years.

Development of a GC-APCI-QTOFMS library for new psychoactive substances and comparison to a commercial ESI library.

Gas chromatography coupled to atmospheric pressure chemical ionization quadrupole time-of-flight mass spectrometry (GC-APCI-QTOFMS) was evaluated for the identification of new psychoactive substances (NPS). An in-house high mass resolution GC-APCI-QTOFMS test library was developed for 29 nitrogen-containing drugs belonging mostly to synthetic stimulants. The library was based on 12 intra-day measurements of each compound at three different collision energies, 10, 20 and 40 eV.

Simultaneous identification and quantification of new psychoactive substances in blood by GC-APCI-QTOFMS coupled to nitrogen chemiluminescence detection without authentic reference standards.

A novel platform is introduced for simultaneous identification and quantification of new psychoactive substances (NPS) in blood matrix, without the necessity of using authentic reference standards. The instrumentation consisted of gas chromatography (GC) coupled to nitrogen chemiluminescence detection (NCD) and atmospheric pressure chemical ionization quadrupole time-of-flight mass spectrometry (APCI-QTOFMS). In this concept, the GC flow is divided in appropriate proportions between NCD for single-calibrant quantification, utilizing the detector's equimolar response to nitrogen, and QTOFMS for accurate mass-based identification.

Early pregnancy cerebral venous thrombosis and status epilepticus treated with levetiracetam and lacosamide throughout pregnancy.

Cerebral venous thrombosis (CVT) is an uncommon cause of stroke, accounting to less than 1% of all strokes. We describe a pregnant woman with a massive CVT in early pregnancy, complicated by status epilepticus. The mother was treated with levetiracetam, lacosamide, and enoxaparin throughout pregnancy.

Compensation of matrix effects in a standard addition method for metformin in postmortem blood using liquid chromatography-electrospray-tandem mass spectrometry.

This work describes a procedure to evaluate matrix effects in a combined dilution and standard addition method (SAM) using liquid chromatography-electrospray-tandem mass spectrometry. The method was validated and applied to an analysis of metformin in postmortem blood samples. The analytical method included protein precipitation with methanol, followed by liquid chromatographic separation of metformin on Gemini NX-C18 reversed-phase column using a gradient consisting of methanol and ammonium acetate at pH 3.

Targeting misuse of 2-amino-N-ethyl-1-phenylbutane in urine samples: in vitro-in vivo correlation of metabolic profiles and development of LC-TOF-MS method.

A phenyethylamine derivative, 2-amino-N-ethyl-1-phenylbutane (2-AEPB), has recently been detected in doping control and drugs-of-abuse samples, and identified as a non-labelled ingredient in a dietary supplement. To facilitate efficient control of this substance we have studied the in vitro metabolic behaviour of 2-AEPB with human liver preparation, compared these results with in vivo pathways in human, and finally propose an analytical strategy to target the potential misuse of 2-AEPB for toxicological, forensic and doping control purposes. The major in vitro formed metabolites originated from desethylation (M1) and monohydroxylation (M2).

Identification of metabolites of fosinopril produced by human and rat liver microsomes with liquid chromatography-mass spectrometry.

Metabolic profiles of prodrug fosinopril and pharmacologically active metabolite fosinoprilat were studied using human or rat liver microsomes and S9 fractions. Metabolites were identified by ultra high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS) using electrospray ionization in the positive and negative ion mode. They were characterized by accurate MS and MS/MS spectra and based on their different fragmentation pathways.

Wastewater analysis reveals regional variability in exposure to abused drugs and opioids in Finland.

Abused drug concentrations were determined in nine Finnish wastewater treatment plants (WWTPs), representing the metropolitan area, university cities and rural towns. In an eight-day study period in August 2012, 24-hour composite influent wastewater samples were collected. Biological markers and census-based information were used to estimate the size of the population served.

Steroid and steroid glucuronide profiles in urine during pregnancy determined by liquid chromatography-electrospray ionization-tandem mass spectrometry.

An ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-MS/MS) method was developed for the analysis of steroids and their glucuronides in urine samples. The method provides high sensitivity and fast analysis, as both steroids and their glucuronides can be analyzed directly without hydrolysis or complex sample preparation. The method was applied in profiling of targeted and nontargeted steroids and steroid glucuronides during pregnancy.

Neurosteroid analysis by gas chromatography-atmospheric pressure photoionization-tandem mass spectrometry.

A new and simple APPI interface employing commercially available hardware is used to combine GC to MS. The feasibility of the method is demonstrated in the analysis of urine samples for neurosteroids as their trimethylsilyl (TMS) derivatives. The effect of different dopants (chlorobenzene, toluene, anisole) on the ionization of the TMS derivatives was investigated.

Determination of Serotonin and Dopamine Metabolites in Human Brain Microdialysis and Cerebrospinal Fluid Samples by UPLC-MS/MS: Discovery of Intact Glucuronide and Sulfate Conjugates.

An UPLC-MS/MS method was developed for the determination of serotonin (5-HT), dopamine (DA), their phase I metabolites 5-HIAA, DOPAC and HVA, and their sulfate and glucuronide conjugates in human brain microdialysis samples obtained from two patients with acute brain injuries, ventricular cerebrospinal fluid (CSF) samples obtained from four patients with obstructive hydrocephalus, and a lumbar CSF sample pooled mainly from patients undergoing spinal anesthesia in preparation for orthopedic surgery. The method was validated by determining the limits of detection and quantification, linearity, repeatability and specificity. The direct method enabled the analysis of the intact phase II metabolites of 5-HT and DA, without hydrolysis of the conjugates.

In silico and in vitro metabolism studies support identification of designer drugs in human urine by liquid chromatography/quadrupole-time-of-flight mass spectrometry.

Human phase I metabolism of four designer drugs, 2-desoxypipradrol (2-DPMP), 3,4-dimethylmethcathinone (3,4-DMMC), α-pyrrolidinovalerophenone (α-PVP), and methiopropamine (MPA), was studied using in silico and in vitro metabolite prediction. The metabolites were identified in drug abusers’ urine samples using liquid chromatography/quadrupole-time-of-flight mass spectrometry (LC/Q-TOF/MS). The aim of the study was to evaluate the ability of the in silico and in vitro methods to generate the main urinary metabolites found in vivo.

Identification of in vitro metabolites of the novel anti-tumor thiosemicarbazone, DpC, using ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry.

Di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) is a promising analogue of the dipyridyl thiosemicarbazone class currently under development as a potential anti-cancer drug. In fact, this class of agents shows markedly greater anti-tumor activity and selectivity than the clinically investigated thiosemicarbazone, Triapine®. However, further development of DpC requires detailed data concerning its metabolism.

Application of electrospray ionization product ion spectra for identification with atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry - a case study with seized drugs.

Product ion spectra obtained with liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI/MS/MS) were applied to the identification of seized drug samples from atmospheric pressure matrix-assisted laser desorption/ionization product ion spectra (AP-MALDI-MS/MS spectra). Data acquisition was performed in the information-dependent acquisition (IDA) mode, and the substance identification was based on a spectral library previously created with LC-ESI/MS/MS using protonated molecules as precursor ions. A total of 39 seized drug samples were analyzed with both AP-MALDI and LC-ESI techniques using the same triple-quadrupole instrument (AB Sciex 4000QTRAP).

Direct analysis of cannabis samples by desorption atmospheric pressure photoionization-mass spectrometry.

Fast analysis of cannabis samples without prior sample preparation or chromatography was performed using desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS). The MS(2) spectra of the molecular ions of tetrahydrocannabinol (THC) and cannabidiol (CBD) formed in DAPPI-MS showed distinct product ions, unlike the protonated molecules formed with other ambient mass spectrometry techniques, making possible the reliable identification of THC from cannabis samples.

Pre-targeting and direct immunotargeting of liposomal drug carriers to ovarian carcinoma.

Background: Epidermal growth factor receptor (EGFR) is overexpressed in many solid tumor types, such as ovarian carcinoma. Immunoliposome based drug targeting has shown promising results in drug delivery to the tumors. However, the ratio of tumor-to-normal tissue concentrations should be increased to minimize the adverse effects of cytostatic drugs.

Mass spectrometric tools for cell and tissue studies.

Mass spectrometry (MS) is a powerful tool for identification and quantitation of organic molecules from various matrices, especially when combined with liquid chromatography (LC). The aim of this review is to present different MS techniques and methods which can be utilized in drug and metabolism studies using cells and tissues. The first part focuses on the use of LC/MS in permeability studies across cell lines as well as in ABC transporter protein experiments.

Impact of probe compound in MRP2 vesicular transport assays.

MRP2 is an efflux transporter that is expressed mainly in the canalicular membrane of hepatocytes, where it expels polar and ionic compounds into the bile. MRP2 is also present in the apical membrane of enterocytes and epithelial cells of proximal tubules of the kidney. Inhibition of MRP2 transport can lead to the accumulation of metabolites and other MRP2 substrates up to toxic levels in these cells.

Comparison of liquid chromatography-microchip/mass spectrometry to conventional liquid chromatography-mass spectrometry for the analysis of steroids.

The feasibility of a microfluidic-based liquid chromatography-electrospray ionization/mass spectrometric system (HPLC-Chip/ESI/MS) was studied and compared to a conventional narrow-bore liquid chromatography-electrospray ionization/mass spectrometric (LC-ESI/MS) system for the analysis of steroids. The limits of detection (LODs) for oxime derivatized steroids, expressed as concentrations, were slightly higher with the HPLC-Chip/MS system (50-300 pM) using an injection volume of 0.5 μL than with the conventional LC-ESI/MS (10-150 pM) using an injection volume of 40 μL.

Impact of protein binding on the analytical detectability and anticancer activity of thymoquinone.

Unlabelled: Thymoquinone (TQ), an active component of Nigella sativa L., is known to have anti-cancer and anti-inflammatory effects; however, no studies on its analytical detection in serum and its protein binding have been published. Using high performance liquid chromatography analysis, we show that the average recovery of TQ from serum is 2.

Rapid screening of drug compounds in urine using a combination of microextraction by packed sorbent and rotating micropillar array electrospray ionization mass spectrometry.

Rationale: Screening of drugs from urine samples can be non-selective or laborous, using either immunological, gas chromatography/mass spectrometry (GC/MS) or liquid chromatography (LC)/MS methods. Therefore, a rapid screening method for selected drugs in urine sample was developed in a proof-of-principle manner, utilizing simple and fast techniques for both sample treatment and sample analysis.

Methods: Sample treament of spiked urine samples was performed with microextraction by packed sorbent (MEPS).

A microfabricated micropillar liquid chromatographic chip monolithically integrated with an electrospray ionization tip.

We present the first monolithically integrated silicon/glass liquid chromatography-electrospray ionization microchip for mass spectrometry. The microchip is fabricated by bonding a silicon wafer, which has deep reactive ion etched micropillar-filled channels, together with a glass lid. Both the silicon channel and the glass lid have a through-wafer etched sharp tip that produces a stable electrospray.

Corn mint (Mentha arvensis) extract diminishes acute Chlamydia pneumoniae infection in vitro and in vivo.

Corn mint ( Mentha arvensis ) provides a good source of natural phenols such as flavone glycosides and caffeic acid derivatives, which may have prophylactic properties against inflammations. This study investigated whether corn mint extract would be beneficial against a universal respiratory tract pathogen, Chlamydia pneumoniae , infection. The extract inhibited the growth of C.