Using complementary mass spectrometric approaches for the determination of methylprednisolone metabolites in human urine

Pozo, Óscar J.; Marcos, Josep; Matabosch, Xavier; Ventura, Rosa; Segura, Jordi

doi:10.1002/rcm.6129

Cited by 30 publications

(69 citation statements)

References 31 publications

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“…Qualitative reduction of reference material was performed based on a procedure described elsewhere (Pozo et al, 2012), in which the carbonyl group is converted in an alcohol moiety. Briefly, 100 ml of reference material (both mephedrone and nor-mephedrone) at 100 mg/ml was evaporated to dryness.…”

Section: Reduction Of Reference Material: Synthesis Of Reference Stanmentioning

confidence: 99%

Mass Spectrometric Evaluation of Mephedrone In Vivo Human Metabolism: Identification of Phase I and Phase II Metabolites, Including a Novel Succinyl Conjugate

et al. 2014

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In recent years, many new designer drugs have emerged, including the group of cathinone derivatives. One frequently occurring drug is mephedrone; although mephedrone was originally considered as a "legal high" product, it is currently banned in most Western countries. Despite the banning, abuse of the drug and seizures are continuously reported. Although the metabolism of mephedrone has been studied in rats or in vitro using human liver microsomes, to the best of our knowledge, no dedicated study with human volunteers has been performed for studying the in vivo metabolism of mephedrone in humans. Therefore, the aim of this study was to establish the actual human metabolism of mephedrone and to compare it with other models. For this purpose, urine samples of two healthy volunteers, who ingested 200 mg mephedrone orally, were taken before administration and 4 hours after substance intake. The discovery and identification of the phase I and phase II metabolites of mephedrone were based on ultra-high-performance liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry, operating in the so-called MS E mode. Six phase I metabolites and four phase II metabolites were identified, four of them not previously reported in the literature. The structure of four of the detected metabolites was confirmed by synthesis of the suggested compounds. Remarkably, a mephedrone metabolite conjugated with succinic acid has been identified and confirmed by synthesis. According to the reviewed literature, this is the first time that this type of conjugate is reported for human metabolism.

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Section: Reduction Of Reference Material: Synthesis Of Reference Stanmentioning

confidence: 99%

Mass Spectrometric Evaluation of Mephedrone In Vivo Human Metabolism: Identification of Phase I and Phase II Metabolites, Including a Novel Succinyl Conjugate

et al. 2014

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“…Any change in this pattern, or the lack of some of these ions means a change in either A or B rings. Particularly a major m/z 171 ion is seen is 6-ene-metabolites [21,30,31]. This ion may result from the fragmentation of the C ring with loss of a water molecule, equivalent to ion m/z 173 for BUD.…”

Section: Detection Of Budesonide Metabolites By Lc-ms/msmentioning

confidence: 99%

“…In the last years, the use of liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) has demonstrated to be useful for the identification of new metabolites of steroids, including glucocorticosteroids [18][19][20][21]. The use of this technology is especially important for metabolic studies of glucocorticosteroids due to the difficulties in obtaining adequate derivatives of polyoxygenated metabolites to make them amenable to GC/MS analysis [22].…”

Section: Introductionmentioning

confidence: 99%

“…The use of this technology is especially important for metabolic studies of glucocorticosteroids due to the difficulties in obtaining adequate derivatives of polyoxygenated metabolites to make them amenable to GC/MS analysis [22]. Recent studies on methylprednisolone and triamcinolone show that LC-MS/MS enables the identification of unreported metabolites [18,21].…”

Section: Introductionmentioning

confidence: 99%

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Identification of budesonide metabolites in human urine after oral administration

Matabosch¹,

Pozo²,

Pérez‐Mañá

et al. 2012

Anal Bioanal Chem

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Budesonide (BUD) is a glucocorticoid widely used for the treatment of asthma, rhinitis, and inflammatory bowel disease. Its use in sport competitions is prohibited when administered by oral, intravenous, intramuscular, or rectal routes. However, topical preparations are not prohibited. Strategies to discriminate between legal and forbidden administrations have to be developed by doping control laboratories. For this reason, metabolism of BUD has been re-evaluated using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with different scan methods. Urine samples obtained after oral administration of 3 mg of BUD to two healthy volunteers have been analyzed for metabolite detection in free and glucuronide metabolic fractions. Structures of the metabolites have been studied by LC-MS/MS using collision induced dissociation and gas chromatography-mass spectrometry (GC/MS) in full scan mode with electron ionization. Combination of all structural information allowed the proposition of the most comprehensive picture for BUD metabolism in humans to this date. Overall, 16 metabolites including ten previously unreported compounds have been detected. The main metabolite is 16α-hydroxy-prednisolone resulting from the cleavage of the acetal group. Other metabolites without the acetal group have been identified such as those resulting from reduction of C20 carbonyl group, oxidation of the C11 hydroxyl group and reduction of the A ring. Metabolites maintaining the acetal group have also been identified, resulting from 6-hydroxylation (6α and 6β-hydroxy-budesonide), 23-hydroxylation, reduction of C6-C7, oxidation of the C11 hydroxyl group, and reduction of the C20 carbonyl group. Metabolites were mainly excreted in the free fraction. All of them were excreted in urine during the first 24 h after administration, and seven of them were still detected up to 48 h after administration for both volunteers.

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“…To find metabolites of MP, a comprehensive list of potential metabolites of the drug was taken from a recently published article where the authors used a mass spectrometer for identification of products originating from all potential metabolic pathways of MP. 28 In the current study, the data obtained from liver sampling were analyzed in negative ionization mode and subjected to a target search of MP metabolites. MP was detected in all liver samples that underwent the used preservation protocol, but it was not detected in the sham (Figure 3).…”

Section: To Determine the Drug Level And Metabolism In Evlp Systemmentioning

confidence: 99%

Low invasive in vivo tissue sampling for monitoring biomarkers and drugs during surgery

Bojko

Goryński

Gómez‐Ríos

et al. 2014

Laboratory Investigation

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The techniques currently used for drug, metabolite, and biomarker determination are based on sample collection, and therefore they are not suitable for repeated analysis because of the high invasiveness. Here, we present a novel method of biochemical analysis directly in organ during operation without need of a separate sample collection step: solid-phase microextraction (SPME). The approach is based on flexible microprobe coated with biocompatible extraction phase that is inserted to the tissue with no damage or disturbance of the organ. The method was evaluated during lung and liver transplantations using normothermic ex vivo liver perfusion (NEVLP) and ex vivo lung perfusion (EVLP). The study demonstrated feasibility of the method to extract wide range of endogenous compounds and drugs. Statistical analysis allowed observing metabolic changes of lung during cold ischemic time, perfusion, and reperfusion. It was also demonstrated that the level of drugs and their metabolites can be monitored over time. Based on the methylprednisolone as a selected example, the impairment of enzymatic properties of liver was detected in the injured organs but not in healthy control. This finding was supported by changes in pathways of endogenous metabolites. The SPME probe was also used for analysis of perfusion fluid using stopcock connection. The evaluation of biochemical profile of perfusates demonstrated potential of the approach for monitoring organ function during ex vivo perfusion. The simplicity of the device makes it convenient to use by medical personnel. With the microprobe, different areas of the organ or various organs can be sampled simultaneously. The technology allows assessment of organ function by biochemical profiling, determination of potential biomarkers, and drug monitoring. The use of this method for preintervention analysis could enhance the decision-making process for the best possible personalized approach, whereas post-transplantation monitoring would be used for graft assessments and fast response in case of organ failure.

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Using complementary mass spectrometric approaches for the determination of methylprednisolone metabolites in human urine

Cited by 30 publications

References 31 publications

Mass Spectrometric Evaluation of Mephedrone In Vivo Human Metabolism: Identification of Phase I and Phase II Metabolites, Including a Novel Succinyl Conjugate

Mass Spectrometric Evaluation of Mephedrone In Vivo Human Metabolism: Identification of Phase I and Phase II Metabolites, Including a Novel Succinyl Conjugate

Identification of budesonide metabolites in human urine after oral administration

Low invasive in vivo tissue sampling for monitoring biomarkers and drugs during surgery

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