Diabetes, a disorder in the control of blood-glucose levels, is one of the most serious metabolic diseases worldwide. Among the investigated technologies for continuous glucose monitoring (CGM), near-infrared spectroscopy (NIR) has received the most attention. There have been many attempts to develop NIR-based CGM systems with promising in-vitro results, but they lacked robustness for in-vivo use. We critically review the application of chemometrics for CGM and the research needed. Pre-processing and multivariate-calibration techniques, which allow exploiting expert knowledge on the potential interferences, are possible solutions. The combination and first overtone bands in the ranges 2050-2300 nm and 1500-1800 nm, respectively, are the most informative regions. We therefore recommended selecting the most informative variables and exploiting the available expert knowledge on known interferences in pre-processing or multivariate calibration to develop an NIR-based CGM sensor for in-vivo use.
The clinical effectiveness of the
important β-lactam class of antibiotics is under threat by the
emergence of resistance, mostly due to the production of acquired
serine- (SBL) and metallo-β-lactamase (MBL) enzymes. To address
this resistance issue, multiple β-lactam/β-lactamase inhibitor
combinations have been successfully introduced into the clinic over
the past several decades. However, all of those combinations contain
SBL inhibitors and, as yet, there are no MBL inhibitors in clinical
use. Consequently, there exists an unaddressed yet growing healthcare
problem due to the rise in recent years of highly resistant strains
which produce New Delhi metallo (NDM)-type metallo-carbapenemases.
Previously, we reported the characterization of an advanced MBL inhibitor
lead compound, ANT431. Herein, we discuss the completion of a lead
optimization campaign culminating in the discovery of the preclinical
candidate ANT2681, a potent NDM inhibitor with strong potential for
clinical development.
A validated ultra-performance liquid chromatography mass spectrometric method (UPLC–MS/MS) was used for the simultaneous quantitation of candesartan (CN) and hydrochlorothiazide (HCT) in human plasma. The analysis was performed on UPLC–MS/MS system using turbo ion spray interface. Negative ions were measured in multiple reaction monitoring (MRM) mode. The analytes were extracted using a liquid–liquid extraction (LLE) method by using 0.1 mL of plasma volume. The lower limit of quantitation for CN and HCT was 1.00 ng/mL whereas the upper limit of quantitation was 499.15 ng/mL and 601.61 ng/mL for CN and HCT respectively. CN d4 and HCT-13Cd2 were used as the internal standards for CN and HCT respectively. The chromatography was achieved within 2.0 min run time using a C18 Phenomenex, Gemini NX (100 mm×4.6 mm, 5 µm) column with organic mixture:buffer solution (80:20, v/v) at a flow rate of 0.800 mL/min. The method has been successfully applied to establish the bioequivalence of candesartan cilexetil (CNC) and HCT immediate release tablets with reference product in human subjects.
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