Journal of mass spectrometry : JMS
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Succinylcholine (SUX) is a routinely used yet potentially lethal depolarizing muscle relaxant, the detection of which poses severe problems to the clinical or forensic analyst: within a few minutes after its in vivo administration, SUX is broken down via succinylmonocholine (SMC) to yield the endogenous substances succinic acid and choline. For quantification of SUX and SMC in biological matrices using mass spectrometric detection, appropriate internal standards, i.e. deuterated analogs of the above substances, are indispensable but not commercially available. Internal standards for both substances were hence tailored to fit the analytical needs. ⋯ SMC-d(3) was produced by esterification of succinic acid anhydride with dimethylaminoethanol, yielding desmethyl-SMC as intermediate product. The latter was then reacted with iodomethane-d(3) to obtain SMC-d(3). (1)H- and (13)C-NMR data support the identity and purity as well as the designated deuteration of both preparations, findings which were further confirmed by FAB-MS as well as HPLC-MS/MS. Owing to a thoughtful design, the obtained substances SUX-d(18) and SMC-d(3) feature different deuteration patterns at their trimethylamine moieties, and thus finally offer the possibility to simultaneously quantify SUX and SMC in clinical as well as forensic samples using isotope dilution mass spectrometry.
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Caspofungin [(CASPO) MK-0991] is the first broad-spectrum anti-fungal agent of the echinocandin class approved for clinical use. Measurement of CASPO levels in blood might help monitor therapy in patients who are critically ill, in particular, if high-dose regimens or combinations of CASPO with other anti-fungals are used. The objective of this study was to develop a fast method for the measurement of CASPO levels in clinical blood samples using liquid chromatography coupled to a triple-quadrupole mass spectrometer. ⋯ Mean intra- and inter-day accuracy was 96.1 +/- 2.2% and 102.5 +/- 2.4%, respectively. Mean intra- and inter-day precision was 7.9 +/- 3.2% and 6.3 +/- 1.8%, respectively. This simple and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method may easily be implemented for monitoring CASPO therapy.
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Glycation of proteins by glucose and formation of end-stage adducts (AGEs, advanced glycation end products) has been implicated in pathological mechanisms associated with diabetic complications, macrovascular disease, chronic and renal insufficiency, Alzheimer's disease, and aging. Of the carbonyl containing compounds involved in this process, alpha-dicarbonyls have particular importance, being established as direct intermediates in the formation of well-known AGEs. The guanidino group, present in arginine residues, suffers direct modifications by sugars and its derivatives, and is considered to be an important chemical basis, targeting the control and inhibition of glycation. ⋯ Moreover, the referred amine-dicarbonyl moieties are formed via (dihydroxyimidazolidine - 2H2O) moieties. The latter (dihydroxyimidazolidine - 2H2O) moieties are formed in high amounts in the larger alkyl-diketonic dicarbonyl reactions. Since these moieties react with dicarbonyl molecules, and react even faster with already modified amine functions, we can foresee that these species may be useful for controlling and inhibiting glycation of larger biomolecules, such as proteins.
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A rapid and sensitive method for the simultaneous confirmatory analysis of three forensic most relevant cannabinoids, Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH), by means of high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS) in human plasma was developed and fully validated. Sample clean-up was performed by automated silica-based solid-phase extraction and the separation was carried out using a PhenylHexyl column (50 x 2 mm i.d., 3 micro m) and acetonitrile-5 mM ammonium acetate gradient elution. Data were acquired with an API 3000 LC/MS/MS system equipped with a turboionspray interface and triple quadrupole mass analyzer using positive electrospray ionization and multiple reaction monitoring. ⋯ The limit of quantitation was 0.8 ng ml(-1) for THC, 0.8 ng ml(-1) for 11-OH-THC and 4.3 ng ml(-1) for THC-COOH and linearity with a correlation coefficient r(2) = 0.999 was achieved up to 100 ng ml(-1) for THC and 11-OH-THC and 500 ng ml(-1) for THC-COOH. The limits of detection were 0.2 ng ml(-1) for THC, 0.2 ng ml(-1) for 11-OH-THC and 1.6 ng ml(-1) for THC-COOH. The developed LC/MS/MS method was also successfully used for the determination of THC-COOH-glucuronide, the phase II metabolite of THC-COOH.
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HIV protease inhibitors are important antiretroviral drugs which have substantially reduced the morbidity and mortality associated with HIV-1 infection. Recent data have shown relationships between plasma concentrations of the protease inhibitors and clinical response, which makes therapeutic drug monitoring valuable. We have developed and validated an assay, using liquid chromatography coupled with electrospray tandem mass spectrometry (LC/MS/MS), for the routine quantification of the six licensed protease inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir) and the pharmacologically active nelfinavir metabolite M8 in plasma. ⋯ Mean accuracies were also between the designated limits (+/-15%). The validated concentration ranges proved to be adequate in daily practice. This robust and fast LC/MS/MS assay is now successfully applied for routine therapeutic drug monitoring and pharmacokinetic studies in our hospital.