High-throughput salting-out assisted liquid/liquid extraction with acetonitrile for the simultaneous determination of simvastatin and simvastatin acid in human plasma with liquid chromatography

Simvastatin (SS) is an effective cholesterol-lowering medicine, and is hydrolyzed to simvastatin acid (SSA) after oral administration. Due to SS and SSA inter-conversion and its pH and temperature dependence, SS and SSA quantitation is analytically challenging. Here we report a high-throughput salting-out assisted liquid/liquid extraction (SALLE) method with acetonitrile and mass spectrometry compatible salts for simultaneous LC-MS/MS analysis of SS and SSA. The sample preparation of a 96-well plate using SALLE was completed within 20 min, and the SALLE extract was diluted and injected into an LC-MS/MS system with a cycle time of 2.0 min/sample. The seamless interface of SALLE and LC-MS eliminated drying down step and thus potential sample exposure to room or higher temperature. The stability of SS and SSA in various concentration ratios in plasma was evaluated at room and low (4 °C) temperature and the low temperature (4 °C) was found necessary to maintain sample integrity. The short sample preparation time along with controlled temperature (2-4 °C) and acidity (pH 4.5) throughout sample preparation minimized the conversion of SS → SSA to ≤0.10% and the conversion of SSA → SS to 0.00% The method was validated with a lower limit of quantitation (LLOQ) of 0.094 ng mL⁻¹ for both SS and SSA and a sample volume of 100 μL. The method was used for a bioequivalence study with 4048 samples. Incurred sample reproducibility (ISR) analysis of 362 samples from the study exceeded ISR requirement with 99% re-analysis results within 100 ± 20% of the original analysis results.     

The effects of selective consonant amplification on sentence recognition in noise by hearing-impaired listeners

Weak consonants (e.g., stops) are more susceptible to noise than vowels, owing partially to their lower intensity. This raises the question whether hearing-impaired (HI) listeners are able to perceive (and utilize effectively) the high-frequency cues present in consonants. To answer this question, HI listeners were presented with clean (noise absent) weak consonants in otherwise noise-corrupted sentences. Results indicated that HI listeners received significant benefit in intelligibility (4 dB decrease in speech reception threshold) when they had access to clean consonant information. At extremely low signal-to-noise ratio (SNR) levels, however, HI listeners received only 64% of the benefit obtained by normal-hearing listeners. This lack of equitable benefit was investigated in Experiment 2 by testing the hypothesis that the high-frequency cues present in consonants were not audible to HI listeners. This was tested by selectively amplifying the noisy consonants while leaving the noisy sonorant sounds (e.g., vowels) unaltered. Listening tests indicated small (～10%), but statistically significant, improvements in intelligibility at low SNR conditions when the consonants were amplified in the high-frequency region. Selective consonant amplification provided reliable low-frequency acoustic landmarks that in turn facilitated a better lexical segmentation of the speech stream and contributed to the small improvement in intelligibility.     

Solutions for the storage and handling of SPINE standard pucks

Currently there is no rack system for the long‐term storage of SPINE pucks in spite of their commercial availability and heavy usage at the ESRF. The only way to store pucks is in transport dewar canisters which presents a number of limitations and drawbacks. Here a simple affordable rack for storing SPINE pucks is described, which we believe is accessible to not only synchrotrons but also both academic and industrial research laboratories.     

PERSISTENCE IN AN AGE-STRUCTURED POPULATION FOR A PATCH-TYPE ENVIRONMENT

A discrete-time model for an age-structured population in a patch-type environment is presented and analyzed. Comparison techniques for difference equations are used to find sufficient conditions for population persistence or extinction. The persistence and extinction theorem is used to define the critical patch number, the threshold for population persistence. Several examples are presented which illustrate the results of the theorems. The model is applied to a watersnake population.