Qualitative and quantitative determination of anaprazole and its major metabolites in human plasma.

Anaprazole is a novel proton pump inhibitor under development for the treatment of gastric and duodenal ulcers. In the present study, an ultra-performance liquid chromatography-ultraviolet detector/quadrupole time-of-flight mass spectrometry method was developed for the metabolic profiling of human plasma after an oral administration of 40 mg anaprazole. The principal metabolic pathways were identified as sulfoxide reduction to thioether (M8-1), dehydrogenation (M21-1), sulfoxide oxidation to sulfone (M16-3), and sulfoxide reduction with O-demethylation to form carboxylic acid (M7-1).

Bioequivalence of paclitaxel protein-bound particles in patients with breast cancer: determining total and unbound paclitaxel in plasma by rapid equilibrium dialysis and liquid chromatography-tandem mass spectrometry.

Paclitaxel protein-bound particles for injectable suspension (nab-paclitaxel) showed many advantages in safety, effectiveness, and convenience. Different from conventional formulations, the bioequivalence evaluation of nab-paclitaxel formulations requires to determine the total amount of paclitaxel in plasma and the unbound paclitaxel to reflect their in vivo disposition. This study aimed to develop an analytical method to quantify the total and unbound paclitaxel in plasma and evaluate the bioequivalence of two formulations of nab-paclitaxel in patients with breast cancer.

Simultaneous determination of imrecoxib and its two active metabolites in plasma of hepatic impairment patients by liquid chromatography-tandem mass spectrometry.

Imrecoxib is a specific inhibitor of cyclooxygenase-2. Its hydroxymethyl (M1) and carboxylic acid (M2) metabolites are the major circulating components in human plasma. It has been demonstrated that the anti-inflammatory activities of M1 and M2 are both equal to the parent drug.

Mechanism of Reductive Metabolism and Chiral Inversion of Proton Pump Inhibitors.

Racemic proton pump inhibitors (PPIs) have been developed into pure enantiomers given superior pharmacokinetic profiles. However, after doses of single enantiomer PPIs, different degrees of chiral inversion were observed. We investigated the relationship between chiral inversion and reductive metabolism of PPIs, as well as the mechanism of reductive metabolism.

Increased Serum IGFBP-1 and Reduced Insulin Resistance After Roux-En-Y Gastric Bypass in Chinese Patients with Type 2 Diabetes: a 6-Month Follow-Up.

Objective: This study aimed to measure changes of insulin-like growth factor binding protein-1 (IGFBP-1) in patients with type 2 diabetes mellitus (T2D) following gastric bypass surgery.

Methods: A total of 10 patients with T2D underwent laparoscopic Roux-en-Y gastric bypass (RYGB) surgery. Patient height, weight, waist circumference, and hip circumference were measured pre- and post-operatively at 6 months after surgery.

[Simultaneous determination of donafenib and its N-oxide metabolite in human plasma by liquid chromatography-tandem mass spectrometry].

Donafenib is the deuterium derivative of sorafenib, and is an anti-tumor drug in clinical trials. An accurate and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of donafenib and its N-oxide metabolite in human plasma. The analytes and internal standards (sorafenib and sorafenib N-oxide) were extracted from plasma by protein precipitation with acetonitrile, and separated on a Gemini C18 (50 mm × 2.

[Determination of anaprazole in human plasma by LC-MS/MS in pharmacokinetic study].

Anaprazole is a proton pump inhibitor clinically used for curing peptic ulcer. A rapid, sensitive and convenient LC-MS/MS method was first established for the determination of anaprazole in human plasma. d(3), (13)C-anaprazole was used as internal standard (IS).

Effect of N-methyl deuteration on metabolism and pharmacokinetics of enzalutamide.

Background: The replacement of hydrogen with deuterium invokes a kinetic isotope effect. Thus, this method is an attractive way to slow down the metabolic rate and modulate pharmacokinetics.

Purpose: Enzalutamide (ENT) acts as a competitive inhibitor of the androgen receptor and has been approved for the treatment of metastatic castration-resistant prostate cancer by the US Food and Drug Administration in 2012.

Population Pharmacokinetic and Covariate Analysis of Apatinib, an Oral Tyrosine Kinase Inhibitor, in Healthy Volunteers and Patients with Solid Tumors.

Background And Objectives: Apatinib is an oral tyrosine kinase inhibitor approved in China for the treatment of patients with advanced metastatic gastric cancer. The approved dosing schedule is 850 mg once daily. The objective of this study was to develop a population pharmacokinetic (popPK) model of apatinib and determine factors that affect its pharmacokinetics.

[A simple method for quantification of tapentadol in dog plasma by liquid chromatography-tandem mass spectrometry and evaluation of the effects of conjugated metabolites on tapentadol].

Tapentadol is a novel drug of opioid pain reliever, which is extensively metabolized primarily through conjugation. Tapentadol glucuronide and tapentadol sulfate are major drug-related metabolites in circulation. The objectives of this study were to develop a simple and rapid method to determine tapentadol and evaluate the effects of conjugated metabolites on tapentadol quantification using liquid chromatography with tandem mass spectrometry in dog plasma.

Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in healthy Chinese volunteers.

Purpose: To investigate the effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in humans.

Methods: Two independent, open-label, randomized, crossover studies were conducted in 24 (12 per study) healthy Chinese volunteers. In Study 1, each volunteer received a single oral dose of 500 mg of nemonoxacin alone or with 1.

[Simultaneous determination of sivelestat and its metabolite XW-IMP-A in human plasma using HPLC-MS/MS].

A simple and rapid method was developed based on high performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to determine sivelestat and its metabolite XW-IMP-A in human plasma. After a simple protein precipitation, the samples and internal standards were analyzed on a C18 column by a gradient elution program. The mobile phase consisted of 30% acetonitrile in methanol and 5 mmol · L(-1) ammonium acetate at a flow rate of 0.

Simultaneous determination of capecitabine and its three nucleoside metabolites in human plasma by high performance liquid chromatography-tandem mass spectrometry.

Capecitabine (Cape) is a prodrug that is metabolized into 5'-deoxy-5-fluorocytidine (DFCR), 5'-deoxy-5-fluorouridine (DFUR), and 5-fluorouracil (5-FU) after oral administration. A liquid chromatography-tandem mass spectrometry method for the simultaneous determination of capecitabine and its three metabolites in human plasma was developed and validated. The ex vivo conversion of DFCR to DFUR in human blood was investigated and an appropriate blood sample handling condition was recommended.

[Determination of γ-aminobutyric acid in human plasma by LC-MS/MS and its preliminary application to a human pharmacokinetic study].

A rapid, sensitive and convenient LC-MS/MS method was developed for the determination of γ-aminobutyric acid (GABA) in human plasma. d2-γ-Aminobutyric acid (d2-GABA) was synthesized as internal standard (IS). After extraction from human plasma by protein precipitation with acetonitrile, all analytes were separated on a Luna HILIC column (100 mm x 3.

Effects of an Al(3+)- and Mg(2+)-containing antacid, ferrous sulfate, and calcium carbonate on the absorption of nemonoxacin (TG-873870) in healthy Chinese volunteers.

Aim: To evaluate the effects of an Al(3+)- and Mg(2+)-containing antacid, ferrous sulfate, and calcium carbonate on the absorption of nemonoxacin in healthy humans.

Methods: Two single-dose, open-label, randomized, crossover studies were conducted in 24 healthy male Chinese volunteers (12 per study). In Study 1, the subjects orally received nemonoxacin (500 mg) alone, or an antacid (containing 318 mg of Al(3+) and 496 mg of Mg(2+)) plus nemonoxacin administered 2 h before, concomitantly or 4 h after the antacid.

Liquid chromatography-tandem mass spectrometry simultaneous determination of repaglinide and metformin in human plasma and its application to bioequivalence study.

A simple, sensitive, selective, and reproducible liquid chromatography-tandem mass spectrometric method was developed for the simultaneous determination of repaglinide and metformin in human plasma using d5-repaglinide and d6-metformin as internal standards (ISs). After a simple protein precipitation using acetonitrile as the precipitation solvent, both analytes and ISs were separated on a Venusil ASB C 18 (150 mm x 4.6 mm, 5 microm) via gradient elution using acetonitrile--10 mmol x L(-1) ammonium acetate as the mobile phase.

Metabolism and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor apatinib in humans.

Apatinib is a new oral antiangiogenic molecule that inhibits vascular endothelial growth factor receptor-2. The present study aimed to determine the metabolism, pharmacokinetics, and excretion of apatinib in humans and to identify the enzymes responsible for its metabolism. The primary routes of apatinib biotransformation included E- and Z-cyclopentyl-3-hydroxylation, N-dealkylation, pyridyl-25-N-oxidation, 16-hydroxylation, dioxygenation, and O-glucuronidation after 3-hydroxylation.

Simultaneous determination of apatinib and its four major metabolites in human plasma using liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

Apatinib, also known as YN968D1, is a novel antiangiogenic agent that selectively inhibits vascular endothelial growth factor receptor-2. Currently, apatinib is undergoing phase II/III clinical trials in China for the treatment of solid tumors. Apatinib is extensively metabolized in humans, and its major metabolites in circulation include cis-3-hydroxy-apatinib (M1-1), trans-3-hydroxy-apatinib (M1-2), apatinib-25-N-oxide (M1-6), and cis-3-hydroxy-apatinib-O-glucuronide (M9-2).

Pharmacokinetics of tacrolimus converted from twice-daily formulation to once-daily formulation in Chinese stable liver transplant recipients.

Aim: To evaluate the pharmacokinetics of tacrolimus in Chinese stable liver transplant recipients converted from immediate release (IR) tacrolimus-based immunosuppression to modified release (MR) tacrolimus-based immunosuppression.

Methods: Open-label, multi-center study with a one-way conversion design was conducted. Eighty-three stable liver recipients (6-24 months post-transplant) with normal renal and stable hepatic function were converted from IR tacrolimus twice-daily treatment to MR tacrolimus once-daily treatment on a 1:1 (mg: mg) total daily dose basis.

Simultaneous determination of dronedarone and its active metabolite debutyldronedarone in human plasma by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study.

Dronedarone is a derivative of amiodarone--a popular antiarrhythmic drug. It was developed to overcome the limiting iodine-associated toxicities of amiodarone. Debutyldronedarone is a major circulating active metabolite of dronedarone in humans.

Liquid chromatography/tandem mass spectrometry method for the quantification of deserpidine in human plasma: Application to a pharmacokinetic study.

A sensitive and rapid liquid chromatography/tandem mass spectrometric (LC/MS/MS) method was developed and validated for the determination of deserpidine in human plasma. The plasma samples were prepared using liquid-liquid extraction (LLE) with ethyl ether-dichloromethane (3:2, v/v). Chromatographic separation was accomplished on an Ultimate XB-C18 column.

Simultaneous determination of 6R-leucovorin, 6S-leucovorin and 5-methyltetrahydrofolate in human plasma using solid phase extraction and chiral liquid chromatography-tandem mass spectrometry.

A selective and rapid method was developed and validated for determination of 6R-leucovorin (LV), 6S-leucovorin and 5-methyltetrahydrofolate (5-MeTHF) in human plasma using stereoselective liquid chromatography-tandem mass spectrometry. All analytes and the internal standard were extracted from plasma by solid phase extraction using Oasis HLB C(18) cartridges. A macrocyclic glycopeptide teicoplanin column was used for chiral separation of LV and 5-MeTHF isomers with NH(4)TFA or NH(4)OAc in methanol as mobile phase.

Quantitative determination of ondansetron in human plasma by enantioselective liquid chromatography-tandem mass spectrometry.

A sensitive and enantioselective method was developed and validated for the determination of ondansetron enantiomers in human plasma using enantioselective liquid chromatography-tandem mass spectrometry. The enantiomers of ondansetron were extracted from plasma using ethyl acetate under alkaline conditions. HPLC separation was performed on an ovomucoid column using an isocratic mobile phase of methanol-5 mM ammonium acetate-acetic acid (20:80:0.

Simultaneous determination of amodiaquine and its active metabolite in human blood by ion-pair liquid chromatography-tandem mass spectrometry.

A sensitive and selective ion-pair liquid chromatography-tandem mass spectrometric method (IP-LC-MS/MS) for the simultaneous determination of amodiaquine (AQ) and its active metabolite, N-desethylamodiaquine (AQm), in human blood has been developed and validated. Pentafluoropropionic acid (PFPA) was applied as ion-pairing reagent in reversed-phase chromatographic separation. The effects of PFPA concentrations and the volume fraction of acetonitrile in the mobile phase on the retention of analytes were investigated on a Venusil MP-C(18) column, and the mobile phase was finally optimized as acetonitrile:water (23:77, v/v) with 0.

Influence of omeprazole on pharmacokinetics of domperidone given as free base and maleate salt in healthy Chinese patients.

Aim: To investigate the influence of omeprazole on the pharmacokinetics of domperidone given as free base and maleate salt.

Methods: An open, randomized, 2-period crossover study with a washout period of 7 d was conducted in 10 healthy Chinese, male patients. In each study period, the patients were administered a single oral dose of 10 mg domperidone as free base or maleate salt on d 1, 20 mg omeprazole twice daily on d 2 and 3, and once on d 4.