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• Unidirectional inversion of ibuprofen enantiomers in Chinese neonates is unclear. • High-throughput UHPLC-MS/MS method to determine ibuprofen enantiomers. • Unexpected pharmacokinetics profile of rac -ibuprofen in Chinese preterm neonates with PDA. Persistent patent ductus arteriosus (PDA) is generally observed in preterm neonates. Oral ibuprofen is the standard treatment for closing PDA in China. To investigate the chiral pharmacokinetics of ibuprofen enantiomers in Chinese premature infants with PDA, a simple, fast, and sensitive analytical enantioselective technology was developed with ultra-performance liquid chromatography (UPLC) – tandem mass spectrometry (MS/MS). Chromatographic separation of (R)-ibuprofen and (S)-ibuprofen was accomplished on a Lux® 3 µm Cellulose-3 (150 mm × 2.0 mm, 3 μm) at a flow rate of 0.2 mL/min within 6 min. UPLC separation was achieved by isocratic elution with a mobile phase consisting of formic acid:water (75:1000000, v/v) and acetonitrile:methanol (1:1, v/v). Only 50 µL of plasma samples were pre-treated with acetonitrile precipitation. Ibuprofen-d 3 was used as an internal standard. The standard curves of both enantiomers were linear over a concentration range of 0.0500 μg/mL to 50.00 μg/mL. The method has been validated for selectivity, carryover effect, lower limit of quantification, precision, accuracy, matrix effect, extraction recovery, dilution integrity, and stability based on the existing guidelines of the National Medical Products Administration, the United States Food and Drug Administration, and the European Medicines Agency. This method has been successfully applied to investigate the pharmacokinetics of ibuprofen enantiomers in 9 preterm infants with PDA. Our results showed that a high chiral inversion ratio of (R)- to (S)-ibuprofen exists in Chinese preterm neonates. Further studies should be conducted to monitor drug concentration following oral administration of ibuprofen and to consider the effect of individual variations and ethnic differences in metabolizing enantiomers of ibuprofen in premature neonates with PDA. [ABSTRACT FROM AUTHOR]

• A UPLC–MS/MS method for quantitative analysis of valsartan, sacubitril and its major metabolite in human plasma, urine and peritoneal dialysis fluid were developed and validated. • This is the first report on a UPLC–MS/MS method for the simultaneous determination of valsartan, sacubitril and LBQ657 concentration in peritoneal dialysis fluid. • This method allowed to better characterize the pharmacokinetic of sacubitril/ valsartan in peritoneal dialysis patients with end-stage renal disease and provided evidence that peritoneal dialysis had an effect on the clearance of sacubitril/valsartan. Sacubitril/valsartan was indicated for the treatment of heart failure and hypertension in patients with end-stage renal disease on peritoneal dialysis therapy. Herein, a rapid, sensitive and robust method based on ultra-liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) was developed and validated for the determination of the concentrations of valsartan, sacubitril and its major metabolite LBQ657 in plasma, urine and peritoneal dialysis fluid. Samples were extracted from various biological fluids using protein precipitation. Extracts were subjected to UPLC–MS/MS with electrospray ionization in positive-ion mode. The developed method was fully validated over a concentration range of 8.00–8000 ng/mL for valsartan, 2.00–2000 ng/mL for sacubitril and 30.0–30,000 ng/mL for LBQ657 in plasma, 2.00–1000 ng/mL for valsartan, 1.00–500 ng/mL for sacubitril and 20.0–10000 ng/mL for LBQ657 in urine, and 0.200–100 ng/mL for valsartan, 0.0400–20.0 ng/mL for sacubitril and 2.00–1000 ng/mL for LBQ657 in peritoneal dialysis fluid. The intra- and inter-day precisions for all analytes in various matrices were less than 12.3%, and the intra- and inter-day accuracies results were all between 88.0% and 109.2%. All analytes were stable for at least 8 h at room temperature (25°C), five freeze–thaw cycles, and 37 days at −40°C and −80°C in plasma, urine and peritoneal dialysis fluid. In conclusion, this developed method is reliable, sensitive and specific for determining the concentrations of valsartan, sacubitril and LBQ657 in plasma, urine and peritoneal dialysis fluid. The assay was available to pilot the pharmacokinetics study of sacubitril/valsartan in patients with end-stage renal disease on peritoneal dialysis, and it could provide evidence that peritoneal dialysis had an effect on the clearance of sacubitril/valsartan. [ABSTRACT FROM AUTHOR]

• A sensitive and robust UPLC–MS/MS method for simultaneous quantification of lidocaine, monoethylglycinexylidide (MEGX) and glycinexylidideme (GX) in human plasma was developed and fully validated. • A simple one-step protein precipitation method was used for the pretreatment of plasma sample. • The fully validated UPLC–MS/MS method was successfully applied to the clinical pharmacokinetics study of lidocaine in liver cancer patients undergoing laparoscopic hepatectomy. • Our results demonstrated that the reasons why the metabolism of lidocaine and MEGX were slightly prolonged might be related to the duration of hepatic blood flow occlusion. Lidocaine, widely used as a local anesthetic, has anti-inflammatory and inhibitory effects on tumor recurrence and metastasis. To investigate the pharmacokinetics of lidocaine in liver cancer patients undergoing laparoscopic hepatectomy, a fast and sensitive analytical technique was developed. The method was adequately validated with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) to simultaneously determine the concentration of lidocaine and its metabolites in plasma. The chromatographic separation was achieved on an Acquity UPLC BEH C 18 column (2.1 × 50 mm, 1.7 µm) by gradient elution with a mobile phase of A (formic acid–water (1:1000, v/v)) and B (formic acid-acetonitrile (1:1000, v/v)). The accuracy and precision were verified within the concentration ranges of 10–5000 ng/mL for lidocaine, 2–1000 ng/mL for monoethylglycinexylidide (MEGX) and 2–500 ng/mL for glycinexylidide (GX). The selectivity, carry-over effect, interference between the analytes and internal standard (IS), precision and accuracy, matrix effect extraction recovery, dilution integrity and stability were satisfactory for the relevant guideline standards. The method was successfully applied to the pharmacokinetic study of lidocaine in liver cancer patients undergoing laparoscopic hepatectomy. After receiving a bolus and continuous infusion, the mean peak concentration of lidocaine was 2097 ng/mL for lidocaine, 336.6 ng/mL for MEGX and 72.66 ng/mL for GX, respectively. The mean peak time was 2.89 h for lidocaine, 5.14 h for MEGX and 9.88 h for GX, respectively. In addition, the mean half-life was 4.19 h for lidocaine and 6.92 h for MEGX. In this study, we found that the metabolism of lidocaine and MEGX might be affected by the hepatic blood flow occlusion or liver injury. [ABSTRACT FROM AUTHOR]

• This strategy combines HRPIF and BS techniques based on DIA and DDA. • The strategy is simple to operate, efficient, and versatile. • This strategy is suitable for Rhei Radix et Rhizoma metabolic analysis in vivo. In traditional Chinese medicine (TCM), components with identical nuclei often share structural similarity, indicating the possibility of similar second-level mass spectrometry (MS/MS) fragments. High-resolution product-ion filter (HRPIF) technique can be utilized to identify metabolites, with similar fragments, in vivo. In principle, this technique applies to TCM; however, its application has been restricted due to the limitations of traditional MS/MS data acquisition. Therefore, a novel analysis strategy, based on data-dependent acquisition (DDA) and data-independent acquisition (DIA) datasets, has been developed for the determination of template product ions and efficient non-targeted identification of TCM-related components in vivo by HRPIF and background subtraction (BS). This DDA-DIA combination strategy, taking Rhei Radix et Rhizoma as a test case, identified 71 anthraquinone prototype components in vitro (36 of which were discovered for the first time), and 45 related components in vivo , confirming glucuronidation and sulfation as the main reactions. The developed strategy could rapidly identify TCM-related components in vivo with high sensitivity, indicating the immense importance of this novel HRPIF data mining technology in TCM analysis. [ABSTRACT FROM AUTHOR]

The neural differentiation of embryonic stem cells (ESCs) is of great significance for understanding of the mechanism of diseases. Histone post-translational modifications (HPTMs) play a key role in the regulation of ESCs differentiation. Here, we combined the stable isotope chemical derivatization with nano-HPLC-mass spectrometry (MS) for comprehensive analysis and quantification of histone post-translational modifications (HPTMs) in mouse embryonic stem cells (mESCs) and neural progenitor cells (mNPCs) that was derived from ESCs. We identified 85 core HPTM sites in ESCs and 78HPTM sites in NPCs including some novel lysine modifications. Our quantitative analysis results further revealed the changes of HPTMs from ESCs to NPCs and suggested effect of combinational HPTMs in the differentiation. This study demonstrates that HPLC–MS-based quantitative proteomics has a considerable advantage on quantification of combinational PTMs and expands our understanding of HPTMs in the differentiation. [ABSTRACT FROM AUTHOR]

The neural differentiation of embryonic stem cells (ESCs) is of great significance for understanding of the mechanism of diseases. Histone post-translational modifications (HPTMs) play a key role in the regulation of ESCs differentiation. Here, we combined the stable isotope chemical derivatization with nano-HPLC-mass spectrometry (MS) for comprehensive analysis and quantification of histone post-translational modifications (HPTMs) in mouse embryonic stem cells (mESCs) and neural progenitor cells (mNPCs) that was derived from ESCs. We identified 85 core HPTM sites in ESCs and 78HPTM sites in NPCs including some novel lysine modifications. Our quantitative analysis results further revealed the changes of HPTMs from ESCs to NPCs and suggested effect of combinational HPTMs in the differentiation. This study demonstrates that HPLC–MS-based quantitative proteomics has a considerable advantage on quantification of combinational PTMs and expands our understanding of HPTMs in the differentiation. [ABSTRACT FROM AUTHOR]