Improved LC-MS/MS method for the determination of 42 neurologically and metabolically important molecules in urine

Abstract

Simultaneous determination of kynurenines, neurotransmitters, pterins and steroids linked to various neurological and metabolic diseases have important diagnostic significance for related pathology and drug monitoring. An improved, sensitive and selective ultra-high performance liquid chromatography coupled to electrospray ionization triple quadrupole mass spectrometric (UHPLC-MS/MS) method, based on our earlier publication, has been proposed for the quantitative measurement of 42 metabolites in human urine. The assay covers a larger number of analytes, uses an advanced, Waters Atlantis T3 chromatographic column and similarly meets the guideline of European Medicines Agency (EMA) on bioanalytical method validation. Analytical performance met all the EMA requirements and the assay covered the relevant clinical concentrations. Linear correlation coefficients were all > 0.998. Intra-day and inter-day accuracy and precision were 87− 118%, 81− 120% and 2-20%, respectively including the lower limit of quantification (LLOQ). The assay is expected to facilitate the diagnosis and allows drug level monitoring from urine.

Autoxidation Kinetics of Tetrahydrobiopterin—Giving Quinonoid Dihydrobiopterin the Consideration It Deserves

“…In order to investigate the effects of the type of buffer, we selected three ammonium-based buffers. Ammonium formate was selected because it is the main constituent of the proposed mobile phase and the most widely used volatile buffer for HPLC-MS separations [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. We also selected ammonium acetate because it is frequently used for the analysis of pterins in biological samples [ 17 ].…”

“…Though strongly suggesting that the first step of H4Bip oxidation led to the release of qH2Bip, these studies, conducted mainly by liquid chromatography coupled to UV–Vis detection, showed that it was very difficult to separate these molecular species [ 24 , 25 ]. Consequently, in the era of the gene therapy of dopamine and serotonin disorders [ 26 ], no current method to determine pterins [ 17 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ] allows to quantify qH2Bip. The available data on qH2Bip remain scarce and conflicting [ 18 , 19 , 20 ].…”

Quantification of clofarabine in urine and plasma by LC-MS/MS: suitable for PK study and TDM in pediatric patients with relapsed or refractory ALL

“…Previous literature 27 reported that renal function and body weight are two important covariates for clearance, therefore, they should be fully considered as components when determining the individual dose of clofarabine. 27 For a basis for optimizing the schedule of clofarabine administration, urine concentration should be standardized by the basal creatinine level. At present, the quantitative method ultimately remains qualitative in that clofarabine can relate only to positive or negative aspects of treatment.…”

“…In recent years, the dilution method is frequently adopted for urine sample preparation because it is not dependent on sample preparation and the effects of the matrix have no impact on the validated LOQs or the ability to detect in urine samples. [25][26][27] In this study, the dilution method was adopted to simplify the preparation of the urine sample and the absolute recovery rates of clofarabine were greater than 85.00% at 5.00, 30.00 and 800.00 ng mL −1 .…”

Role of the kisspeptin-KISS1R axis in the pathogenesis of chronic kidney disease and uremic cardiomyopathy

“…The levels of serum uremic toxins were measured according to previously published methodologies using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) [ 34 , 41 , 42 ]. MRM transition of indoxyl sulfate was 211.9/131.9 using − 50 V as declustering potential and − 25 V as collision energy, retention time: 11.48 min.…”