The preparation and evaluation of human whole blood control materials for point-of-care glucose testing / 中华检验医学杂志

Objective:To prepare the control materials of point-of-care(POC) glucose testing and evaluate their homogeneity, stability and matrix effects.Methods:The high, medium and low concentration control materials were prepared from patient leftover whole blood, which was centrifuged, fixed, washed, filtered, and aliquoted. The homogeneity and stability of the control materials were evaluated according to CNAS (China National Accreditation Service for Conformity Assessment, CNAS) GL29:2010"Reference materials-General and statistical principles for certification". The control materials were used to evaluate the matrix effects in POC glucose detection systems by Deming regression, according to the Clinical and Laboratory Standards Institute (CLSI) EP14-A3. Meanwhile, these control materials were used as the internal quality control, and their coefficients of variation ( CV) were calculated. One-way ANOVA and t-Test were used to analyze the results. Results:The homemade materials at three concentrations showed good homogeneity[ F< F0.05(9, 20)]. When the control materials were stored at 2-8 ℃, the stable phases for the opened and closed bottles were 10 days and 15 days, respectively, and there was no statistically significant difference between the results of the first day( P>0.05). The control materials at three concentrations also showed good applicability and there were no matrix effects in 10 POC glucose systems. When the control materials were detected in the internal quality control, the CVs of the high, medium and low concentrations were 0.63%, 0.66% and 1.65%, respectively, which were all below 7.5%. Conclusions:The homemade human control materials of POC glucose testing showed good homogeneity, stability and applicability. They met the requirements of quality control in hospital settings, which provided a good application prospect of the quality management of POC glucose testing.

Three-dimensional aspects of formulation excipients in drug discovery:a critical assessment on orphan excipients, matrix effects and drug interactions / 药物分析学报

Formulation/pharmaceutical excipients play a major role in formulating drug candidates, with the ob-jectives of ease of administration, targeted delivery and complete availability. Many excipients used in pharmaceutical formulations are orphanized in preclinical drug discovery. These orphan excipients could enhance formulatability of highly lipophilic compounds. Additionally, they are safe in preclinical species when used below the LD50 values. However, when the excipients are used in formulating compounds with diverse physico-chemical properties, they pose challenges by modulating study results through their bioanalytical matrix effects. Excipients invariably present in study samples and not in the cali-bration curve standards cause over-/under- estimation of exposures. Thus, the mechanism by which excipients cause matrix effects and strategies to nullify these effects needs to be revisited. Furthermore, formulation excipients cause drug interactions by moderating the pathways of drug metabolizing en-zymes and drug transport proteins. Although it is not possible to get rid of excipient driven interactions, it is always advised to be aware of these interactions and apply the knowledge to draw meaningful conclusions from study results. In this review, we will comprehensively discuss a) orphan excipients that have wider applications in preclinical formulations, b) bioanalytical matrix effects and possible ap-proaches to mitigating these effects, and c) excipient driven drug interactions and strategies to alleviate the impacts of drug interactions.

Research Progresses of Determination of Perfluorinated Compounds in Environmental Water and Solid Samples / 分析化学

Perfluorinated compounds (PFCs), a group of persistent organic pollutants, have been widely detected in environmental media and posed great threat to human health. The researches on environmental pollution and health concern of PFCs are the hotspot areas. Because PFCs contain lots of homologs and isomers which are detected at trace levels (ng/g or μg/L) in environment, advanced and reliable analytical methods for determination of PFCs in environment are urgently needed. At present, studies on analytical methods of trace PFCs in environmental samples have been widely carried out in China and abroad. However, systematic review on the sample pretreatment, analytical method, and matrix effect of PFCs determination in complex environmental matrixes is relatively scarce. Therefore, this paper reviews the pretreatment methods, martix effects, and detection techniques (especailly isomers) of PFCs in environment samples (water, sediment/sluge, soil and plant). We hope that this review may provide valuable reference for the enviromental researches on PFCs.

Quantification of amlodipine in human plasma by LC-MS/MS method: elimination of matrix effects by improving chromatographic conditions / 药学学报

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of amlodipine in human plasma. The influence of alkalizer, extraction solvent and the chromatographic conditions on the matrix effects was investigated. The stable isotope-labeled amlodipine (amlodipine-d4) was used as an internal standard. Sample preparation involved simple liquid-liquid extraction procedure using methyl tertiary butyl ether. Chromatographic separation was achieved on a Welch Ultimate XB-C18(100 mm×2.1 mm, 3 μm) column with acetonitrile/2 mmol·L-1 ammonium formate (pH 3.0) under gradient condition at a flow rate of 0.6 mL·min-1. Detection was performed using electrospray ionization (ESI) in positive ion multiple reaction monitoring (MRM) mode. The linear range of the analyte was 0.1-20.0 μg·L-1, with the lower limit of quantitation (LLOQ) of 0.1 μg·L-1. The matrix factor for low, medium, high concentration quality control samples and internal standard was (93.9±1.8)%, (95.8±4.9)%, (93.9±1.5)% and (97.9±5.3)%, respectively. The method showed excellent specificity, linearity, intra-day and inter-day accuracy and precision, extraction recovery and stability, according to the CFDA guidance for bioanalytical method validation. The matrix effect was significantly improved through optimizing the chromatographic conditions. This economical, simple, robust, sensitive and specific method is entirely able to meet the requirement of the determination of amlodipine in human plasma samples obtained from bioequivalence studies.

Participating in the evaluation of combined value assignment of Cystatin-C as a national standard material candidate / 国际检验医学杂志

Objective As a collaborator of Beijing Institute of Medical Device Testing for value assignment of state standard ma-terial candidate Cystatin-C ,we have used the internationally accepted reference material to assign value for state standard material candidate Cystatin-C ,and help Beijing Institute of Medical Device Testing get Cystatin-C national standard material certificate . Methods According to the target value and operational procedure of international reference material ERM-DA471 ,We have tested 6 dilutions of standard material candidate Cystatin-C on calibrated Hitachi 7180 immunoassay system .Results The results demon-strate good repeatability and commutability ,and have been accepted in calculating the final value for the candidate standard materi-al ,our data has assisted Beijing Institute of Medical Device Testing in passing the criteria and obtaining Cystatin-C national standard material certificate .Conclusion Compared to the data from all participating collaborators ,our results hit right on the target value , and no significant matrix effects have been observed .

Study of stabilization of the enzyme activity of ALT and the matrix effects of betaine / 中华检验医学杂志

Objective To investigate the stabilization of betaine on the enzyme activity of ALT in human serum at different temperatures, and to evaluate the matrix effects of human serum with betaine among different analytical systems. Methods The enzyme activity of ALT in human serums with l mol/L betaine stored at 37 ℃, 25 ℃, 4 ℃ and - 20 ℃ respectively were measured. The matrix effect experiment was carried out according to the procedures specified in Clinical and Laboratory Standards Institute (CLSI)document EP14-A. Four analytical systems were the candidates for evaluation, and Roche Diagnostics (Roche)-Hitachi analytical system served as the reference system. The enzyme activity of ALT of 40 patient specimens and 3-level specimens ( high, medium and low) with 1 mol/L betaine were measured using the evaluated methods and the reference method respectively. The linear regression analysis was performed to compare the mean y value of 3-level specimens with the statistically defined limits ( the two-tailed 95% prediction interval) derived from 40 patient specimen data. Results The enzyme activity of ALT could be stabilized with betaine in serum, which remained to be 99% for 48 h at 37 ℃, 98% for4 d at 25 ℃, 97%for 4 weeks at 4 ℃, and 99% for 4 months at - 20 ℃. The enzyme activity of control serum decreased to 42%, 86%, 71%, 79% respectively. The mean y values of three specimens with the betaine were within the 95% prediction interval of the estimated mean y values, which suggested no obvious matrix effects in serum. Conclusion Betaine can be used in the development of enzyme ALT calibrator as its stabilizer.