Application of Capillary Electrophoresis for Determination of Inorganic Analytes in Waters

Aside from HPLC and GC, capillary electrophoresis (CE) is one of the most important techniques for high-performance separations in modern analytical chemistry. Its main advantages are the possibility of using different detection techniques, the possibility of in-capillary sample processing for preconcentration or derivatization, and ease of instrumental miniaturization down to the microfluidic scale. Those features are utilized in the separation of macromolecules in biochemistry and in genetic investigations, but they can be also used in determinations of inorganic ions in water analysis. This review, based on about 100 original research works, presents applications of CE methods in water analysis reported in recent decade, mostly regarding conductivity detection or indirect UV detection. The developed applications include analysis of high salinity sea waters, as well as analysis of other surface waters and drinking waters.

Electrophoretic Determination of Symmetric and Asymmetric Dimethylarginine in Human Blood Plasma with Whole Capillary Sample Injection

Asymmetric and symmetric dimethylarginines are toxic non-coded amino acids. They are formed by post-translational modifications and play multifunctional roles in some human diseases. Their determination in human blood plasma is performed using capillary electrophoresis with contactless conductivity detection. The separations are performed in a capillary covered with covalently bonded PAMAPTAC polymer, which generates anionic electroosmotic flow and the separation takes place in the counter-current regime. The background electrolyte is a 750 mM aqueous solution of acetic acid with pH 2.45. The plasma samples for analysis are treated by the addition of acetonitrile and injected into the capillary in a large volume, reaching 94.5% of the total volume of the capillary, and subsequently subjected to electrophoretic stacking. The attained LODs are 16 nm for ADMA and 22 nM for SDMA. The electrophoretic resolution of both isomers has a value of 5.3. The developed method is sufficiently sensitive for the determination of plasmatic levels of ADMA and SDMA. The determination does not require derivatization and the individual steps in the electrophoretic stacking are fully automated. The determined plasmatic levels for healthy individuals vary in the range 0.36–0.62 µM for ADMA and 0.32–0.70 µM for SDMA.

Generating the atomic pair distribution function without instrument or emission profile contributions

A method for generating the atomic pair distribution function (PDF) from powder diffraction data by the removal of instrument contributions, such as Kα2 from laboratory instruments or peak asymmetry from neutron time-of-flight data, has been implemented in the computer programs TOPAS and TOPAS-Academic. The resulting PDF is sharper, making it easier to identify structural parameters. The method fits peaks to the reciprocal-space diffraction pattern data whilst maximizing the intensity of a background function. The fit to the raw data is made `perfect' by including a peak at each data point of the diffraction pattern. Peak shapes are not changed during refinement and the process is a slight modification of the deconvolution procedure of Coelho [J. Appl. Cryst. (2018), 51, 112–123]. Fitting to the raw data and subsequently using the calculated pattern as an estimation of the underlying signal reduces the effects of division by small numbers during atomic scattering factor and polarization corrections. If the peak shape is sufficiently accurate then the fitting process should also be able to determine the background if the background intensity is maximized; the resulting calculated pattern minus background should then comprise coherent scattering from the sample. Importantly, the background is not allowed complete freedom; instead, it comprises a scan of an empty capillary sample holder with a maximum of two additional parameters to vary its shape. Since this coherent scattering is a calculated pattern, it can be easily recalculated without instrumental aberrations such as capillary sample aberration or Kα2 from laboratory emission profiles. Additionally, data reduction anomalies such as incorrect integration of data from two-dimensional detectors, resulting in peak position errors, can be easily corrected. Multiplicative corrections such as polarization and atomic scattering factors are also performed. Once corrected, the pattern can be scaled to produce the total scattering structure factor F(Q) and from there the sine transform is applied to obtain the pair distribution function G(r).

Point-of-care measurement of clozapine concentration using a finger-stick blood sample

Background: The use of clozapine demands regular monitoring of clozapine plasma concentrations and of white blood cell parameters. The delay between sending blood samples for analysis and receiving the results hinders clinical care. Point-of-care testing (POCT) can provide drug assay results within a few minutes. Aim: This study aimed to investigate the utility of a novel point-of-care device that can measure clozapine concentrations using capillary blood samples collected via a finger stick. Method: During a five-week period starting in June 2019 eligible patients were asked to provide a finger-stick capillary sample in addition to their usual venous blood sample. Samples were analysed by the novel point-of-care device and by the standard laboratory method. Capillary blood samples were tested by the MyCare™ Insite POCT analyser, and a quantitative measurement of clozapine concentration was provided within six minutes. Results: A total of 309 patients agreed to measurements by the two methods. Analysis revealed clozapine concentrations in venous blood as determined by the laboratory method ranged from 20 to 1310 ng/mL and by POCT from 7 to 1425 ng/mL. There was a strong positive correlation ( R = 0.89) between the results from the venous and the capillary sample methods. The slope of the association between standard assay and MyCare™ Insite was 1.0 with an intercept of –21 ng/mL, indicating minimal bias. Conclusion: Clozapine concentrations can be accurately measured at the point of care using capillary blood samples collected via a finger stick. This approach may be more acceptable than venous sampling to patients and, with almost instant results available, more useful to clinicians.

Using a fingerstick test for haematological monitoring in patients treated with clozapine

Background Treatment with clozapine requires regular blood monitoring in order to minimise the risk of agranulocytosis. The demands on patients and clinicians associated with monitoring may be reduced by using point-of-care, as opposed to lab-based assessments. We assessed the utility of a device that can measure white blood cell (WBC) and neutrophil counts by capillary fingerstick blood. Method The performance of a small, portable device (HemoCue® WBC DIFF System) was compared with that of a widely used laboratory analyser (ADVIA® 2120i) for measuring WBC and neutrophil counts. Patients with schizophrenia who were being treated with clozapine ( n = 201) provided a fingerstick capillary sample and a venous sample for the respective assays. Results WBC counts and neutrophil counts from venous blood as determined by ADVIA 2120i, ranged from 3.0 × 109/l to 19.5 × 109/l, and 1.2 × 109/l to 15.9 × 109/l, respectively. There was a strong correlation between the results from venous and the capillary sample methods (WBC: R = 0.89, neutrophil: R = 0.92). By Passing–Bablok regression analysis, the slope of the association between ADVIA® 2120i and HemoCue WBC DIFF for WBC was 1.0 [95% confidence interval (CI) 0.944–1.086], with intercept at −0.9 (95% CI −1.43 to −0.45). For neutrophils, the slope was 0.870 (95% CI 0.817–0.923), with intercept at −0.19 (95% CI −0.43 to 0.02). Overall, mean biases of −0.95 × 109/l for WBC, and −0.91 × 109/l for neutrophils were observed for the capillary blood method compared with the venous blood method. Below the clinical cutoff intervals for clozapine monitoring WBC (<3.5 × 109/l) and neutrophils (<1.5 × 109/l) these biases were −1.1 × 109/l for WBC, and −0.25 × 109/l for neutrophils. Conclusion Results from the capillary blood HemoCue WBC DIFF analyser compared well with the venous blood ADVIA 2120i analyser for determining WBC and neutrophil counts. There was a slight overall bias, with the capillary method reporting lower values for both measures. Fingerstick point-of-care analysis is suitable for monitoring blood counts in patients on clozapine, although confirmatory standard venous testing is recommended for test results falling below accepted thresholds.

Preanalytical Challenges During Capillary Fingerstick Sampling Preclude Its Widespread Use in Adult Hospitalized Patients

Objectives Patient compliance with laboratory testing is one of the most underrecognized challenges in developing a treatment plan for acute and chronically ill patients. The ability to offer alternatives to standard venipuncture blood draws would greatly increase a laboratory’s ability to provide testing to patients and health care providers. Methods We performed a prospective observational study on paired venous and fingerstick capillary blood samples from admitted patients undergoing vancomycin therapy. Paired specimens were analyzed for vancomycin and a basic metabolic panel (BMP: calcium, carbon dioxide, chloride, potassium, sodium, creatinine, glucose, serum urea nitrogen) on the core laboratory’s automated chemistry and immunochemistry platforms. Results A total of 59 paired fingerstick and venous blood specimens from 56 unique inpatients were analyzed. Paired samples were comparable for all the analytes tested with the exception of bicarbonate and potassium, which were significantly different among the capillary sample group. Patients required multiple fingers be lanced in 15% of cases to obtain sufficient blood to carry out the testing. Capillary sample rejection rates due to insufficient volumes were as high as 30% in the initial 30 patients enrolled in the study. Conclusions Vancomycin and the BMP, with the exception of potassium and bicarbonate, were determined to be analytically comparable. However, significant preanalytical issues should preclude laboratories and providers from more widespread adoption of fingerstick-derived capillary blood as an alternative sampling method except in the most extenuating of circumstances.

Impacts of Seasonal Malaria Chemoprevention on Malaria Burden among under Five-Year-Old Children in Borno State, Nigeria

Malaria disproportionately affects all ages with a high burden among children below five years. Thus, control measures are deployed including Seasonal Malaria Chemoprevention (SMC). The present study assessed the impacts of SMC on malaria burden among subjects aged 3–59 months in Borno State, Nigeria. Twenty (20) clusters were randomly selected from accessible 16 Local Government Areas (LGAs) of Borno State, Nigeria, and SMC was deployed in 10 of the clusters by administering a full dose of amodiaquine plus sulfadoxine-pyrimethamine at monthly intervals for 4 months consecutively. Three hundred and ninety-nine children were enrolled in the study. A structured questionnaire was used to obtain demographic and malaria-related data. Thick blood smear, thin blood smear, and capillary sample were collected two weeks after the 4th cycle of SMC. The prevalence of malaria and anaemia was determined among the subjects and for the clusters. The proportions of the female (46.4%; 185/399) and male (53.6%; 214/399) subjects were similar (p>0.05) with subjects aged 24–47 months (35.8%; 143/399) accounting for the highest proportion (p<0.05). Malaria prevalence was 10.3% (41/399) and was higher among non-SMC subjects (15.9%; 31/195) than among SMC subjects (4.9%; 10/204) (p<0.05, df = 1, χ2 = 10.8). Malaria prevalence was higher in non-SMC clusters (80.0%; 8/10) than in SMC clusters (30.0%; 3/10) (p<0.05, df = 1, χ2 = 40.5). The mean haematocrit of the 399 subjects was 34.0 ± 5.3% with an anaemia prevalence of 18.1% (72/399). The mean haematocrit was higher among SMC subjects (35.4 ± 5.0% vs. 33.1 ± 4.2%; p<0.05) while anaemia prevalence was higher among non-SMC subjects (21.5% vs. 14.6%; p<0.05, df = 1, χ2 = 2.8). Of the SMC subjects, 4.9% reported adverse drug reactions. SMC is safe and significantly reduced malaria burden among children in Borno State, and thus, the measure could be deployed in the state for effective malaria control.

Testing the flow-through capillary for the study of re-solvation processes in pharmaceutical compounds

This paper describes a new flow-through capillary sample holder that allows the in situ study of re-solvation processes. The holder can be aligned to the goniometer's center using two perpendicular micrometric tables that move in y and z directions. The re-solvation of two ibrutinib solvates of anisole and fluorobenzene was tested using the holder to show the practical application of this technique.

Effectiveness of diabetes in pregnancy study group India diagnostic criterion in detecting gestational diabetes mellitus: a rural Bangalore study

Background: The oral glucose tolerance test (OGTT) is considered the current standard for diagnosis of gestational diabetes mellitus (GDM). International association of diabetes and pregnancy study groups (IADPSG) recommends OGTT, with fasting, one-hour and two-hour venous blood samples drawn after intake of 75g oral glucose. In the Indian context, diabetes in pregnancy study group in India (DIPSI) recommends glucose challenge test (GCT), where 75 g glucose is given irrespective of the fasting state, and a single venous sample is drawn after two-hour. Diagnosis of GDM is made, if any cut-off value is met or exceeded. This prospective study was conducted to compare the DIPSI and IADPSG criteria for diagnosis of GDM.Methods: Pregnant women between 24 to 28 weeks of gestation were subjected to non-fasting GCT. Capillary sample were also drawn simultaneously using Accu check active glucometer. These women were counselled to undergo a standard 75gram OGTT, within a week of recruitment.Results: According to IADPSG criteria, 17.6% (18/102) of our participants had GDM, as compared to 19.6% (20/102) by DIPSI criteria using venous samples, and 25.3% (25/99) by capillary sample method. Sensitivity and specificity of GCT using venous sample was 72.22% and 91.67%, and using capillary sample was 70.59% and 84.15% respectively. DIPSI criteria using venous samples wrongly labelled 8.3% women as GDM, and capillary samples wrongly labelled 15.9% women as GDM. More importantly DIPSI criteria using venous samples labelled 27.8% women as false-negative and capillary samples labelled 29.4% women as false-negative for GDM. Almost one quarter of women with GDM will be missed if DIPSI criteria is used as a universal screening modality.Conclusions: We suggest that the IADPSG criteria be used for diagnosis of GDM in antenatal women in India.