Dataset Information

GNPS - Upload positive mode data only from urine antihypertensive screening paper

ABSTRACT: Note that this only contains the positive fragmentation mode data obtained in the project filtered from the posneg combined mode from MSV000082971 - see further details there.

OTHER RELATED OMICS DATASETS IN: MTBLS307

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Justin van der Hooft

PROVIDER: MSV000083528 | GNPS | Tue Mar 05 08:04:00 GMT 2019

REPOSITORIES: GNPS

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Urinary antihypertensive drug metabolite screening using molecular networking coupled to high-resolution mass spectrometry fragmentation.

van der Hooft Justin J J JJ Padmanabhan Sandosh S Burgess Karl E V KE Barrett Michael P MP

Metabolomics : Official journal of the Metabolomic Society 20160705

<h4>Introduction</h4>Mass spectrometry is the current technique of choice in studying drug metabolism. High-resolution mass spectrometry in combination with MS/MS gas-phase experiments has the potential to contribute to rapid advances in this field. However, the data emerging from such fragmentation spectral files pose challenges to downstream analysis, given their complexity and size.<h4>Objectives</h4>This study aims to detect and visualize antihypertensive drug metabolites in untargeted metab ...[more]

PMID: 27471437

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Project description:Urine MS/MS data acquired to test Molecular Networking as tool for drug screening in human urine to assist in drug adherence monitoring. Samples from a antihypertensive drug adherence human cohort were retroperspectively selected to test how many commonly prescribed antihypertensives and other over-the-counter drugs were picked up by Molecular Networking in 26 extracts. In addition, several endogenous molecular families were also annotated. Data was obtained in positive and in negative ionization mode on a Thermo Scientific Q-Exactive Orbitrap instrument, using stepped collision energy HCD fragmentation in a data-dependent-manner (DDA). Urine samples from anonymized human volunteers were used from a clinical sample set in the Glasgow Polyomics archive. These samples were obtained as part of a trial for which ethical approval was applied for through the Multi-centre Research and Ethics Committee (MREC), which was granted by the Scottish MREC and (with MREC N°06/MRE00/106). Informed consent was obtained from all individual study participants. Spot urine samples were obtained from the cohort of elderly hypertensive patients upon their first admission in the clinic. Urine extracts of 26 patients were selected as follows: diagnosed with hypertension, taking in a variety of different antihypertensive drugs (i.e., different drug classes), and availability of the sample extract in the Glasgow Polyomics archive. The resulting subject’s age range spanned from 42 to 87; 15 were male, 11 female; 4 were smokers; 5 were reported to have diabetes; and each reportedly took from 2 to 7 different classes of antihypertensive drugs. Full details also on data acquisition and analysis can be found in Van der Hooft et al. 2016, Metabolomics. Chromatography and Mass Spectrometry details: The samples were analysed using a Thermo Scientific Ultimate 3000 RSLCnano system (Thermo Scientific, CA, USA). The pHILIC separation was performed with a SeQuant ZIC-pHILIC column (150 x 4.6 mm, 5 microm) equipped with the corresponding pre-column (Merck KGaA, Darmstadt, Germany) - the column temperature was maintained at 25 C. A linear biphasic LC gradient was conducted from 80% B to 20% B over 15 min, followed by a 2 min wash with 5% B, and 8 min re-equilibration with 80% B, where solvent B is acetonitrile and solvent A is 20 mM ammonium carbonate in water. The flow rate was 300 microL/min, column temperature was held at 25 C, injection volume was 10 microL, and samples were maintained at 4 C in the autosampler. MS equipment and settings used: The LC system was coupled to a Thermo Scientific Q-Exactive Orbitrap mass spectrometer equipped with a HESI II interface (Thermo Scientific, Hemel Hempstead, UK). The set up was calibrated (Thermo calmix) in both ionization modes and tuned for the lower m/z range before analysis. Full scan (MS1) data was acquired in positive and negative switching mode in profile mode at 35,000 resolution (at m/z 200) using 1 microscan, an AGC target of 106 cts, a maximum injection time of 250 ms, with spray voltages +3.8 and -3.0 kV, capillary temperature 320 C, heater temperature of 150 C, sheath gas flow rate 40 a.u., auxiliary gas flow rate 5 a.u., sweep gas flow rate 5 a.u, a full scan mass window of 70-1050 m/z, and using m/z 74.0964 (+) and m/z 112.98563 (-) as locking masses. Fragmentation data (LC-MS/MS) was obtained in positive and negative ionization combined and separate fragmentation modes as described in (van der Hooft et al 2016). Briefly, for separate mode, a duty cycle consisted of one full scan (MS1) event and one Top5 (or Top10) MS/MS (MS2) fragmentation event, with full scan (MS1) resolution (at m/z 200) was set to 70,000, the AGC target set to 1 x 106, and the maximum injection time set to 120 ms. MS/MS (MS2) resolution (at m/z 200) was set to 17,500, the AGC target set to 2 x 105, MS/MS maximum injection time was set to 80 ms and the underfill ratio was set to 10 %, with a resulting intensity threshold of 2.5 × 105 cts. For combined mode, a duty cycle consisted of two of the above events in positive and negative ionization mode with the following modifications: full scan (MS1) resolution (at m/z 200) was set to 35,000, MS/MS resolution was set to 35,000, the AGC target was set to 1 x 105, and the maximum MS/MS filling time was set to 120 ms with an underfill ratio of 20%, resulting in an intensity threshold of 1.7 x 105. Further settings were as specified for full scan analysis above.

Project description:Background As congenital cytomegalovirus (CMV) infection causes significant clinical consequences not only at birth but also later as neurological sequelae, it is critical to establish a strategy for screening congenitally infected newborns. Previous studies have identified an insufficient sensitivity in screening methods based on the use of dried blood spots (DBSs). Objectives To evaluate the feasibility of the authors' recently developed method for large-scale screening for congenital CMV infection and to identify risk factors for congenital infection. Methods More than 21 000 newborns were enrolled at 25 sites in six geographically separate areas of Japan. Urine was collected onto filter cards placed in the diapers, which were then analysed by quantitative PCR using the filter disc directly as a template. Clinical and physical findings of the newborns were extracted from their medical records. CMV strains from the cases and their siblings were genetically compared. Viral loads in DBSs obtained from some of the cases were compared with those in the urine filters. Results Congenital CMV infection was identified in 0.31% (95% CI 0.24% to 0.39%) of the newborns, and 30% of the cases (20/66) had typical clinical manifestations and/or showed abnormalities in brain images at birth. Although the positive predictive value of our screening was 94%, the lack of any comparison with a gold standard assay prevented calculation of the negative predictive value. Almost two-thirds of the cases had siblings, a significantly higher frequency than for uninfected newborns. Most of the cases (21/25) excreted CMV strains identical to those of their siblings. CMV DNA was undetectable in three out of 12 retrievable DBS specimens. Conclusions Implementation of an effective large-scale screening programme for congenital CMV infection is feasible. Siblings are the major risk factor for congenital CMV infection, which emphasises the need for education of mothers-to-be as well as vaccine development.