Needle-in-needle electrochemical sensor for in-vivo monitoring of anticancer drug etoposide.

Therapeutic drug monitoring (TDM) serves as a potent tool for adjusting drug concentration within a reasonable range. However, continuous monitoring of anticancer drugs in-vivo presents a significant challenge. Herein, we propose a needle-in-needle electrochemical sensor based on an acupuncture needle electrode, capable of monitoring the anticancer drug etoposide in the peritoneal cavity of living rats. The acupuncture needle was modified with Au nanoparticles and etoposide-templated molecularly imprinted polymer (MIP), resulting in high sensitivity and selectivity in the electrochemical detection of etoposide. The modified acupuncture needle (0.16 mm diameter) was anchored inside a syringe needle (1.40 mm diameter), allowing the outer syringe needle to protect the modified materials of the inner acupuncture needle during skin piercing. Due to the unique needle-in-needle design, high stability was obtained during in-vivo etoposide monitoring. Connecting to a smartphone-controlled portable electrochemical workstation, the needle-in-needle sensor offers great convenience in point-of-care TDM. Moreover, the electrode materials on the acupuncture needle were carefully characterized and optimized. Under the optimized conditions, low detection limits and wide linear range were achieved. This work provides new insights into acupuncture needle electrochemical sensors and further expands the feasibility for real-time and in-vivo detection.

Standardization and validation of a high-efficiency liquid chromatography with a diode-array detector (HPLC-DAD) for voriconazole blood level determination. / Estandarización y validación de un método de cromatografía líquida de alta eficiencia con detector de arreglo de diodos (HPLC-DAD) para la determinación de niveles sanguíneos de voriconazol

INTRODUCTION: A specialized service for antifungal blood level determination is not available in Colombia. This service is essential for the proper follow-up of antifungal therapies. OBJECTIVE: To standardize and validate a simple, sensitive, and specific protocol based on high-performance liquid chromatography with a diode array detector for voriconazole blood level quantification. MATERIALS AND METHODS: We used an Agilent HPLC™ series-1200 equipment with a UVdiode array detector with an analytical column Eclipse XDB-C18 and pre-column Eclipse- XDB-C18 (Agilent). We used voriconazole as the primary control and posaconazole as an internal control. We performed the validation following the Food and Drug Administration (FDA) recommendations. RESULTS: The best chromatographic conditions were: Column temperature of 25°C, UV variable wavelength detection at 256 nm for voriconazole and 261 nm for posaconazole (internal standard); 50 µl of injection volume, 0,8 ml/min volume flow, 10 minutes of run time, and mobile phase of acetonitrile:water (60:40). Finally, retention times were 3.13 for voriconazole and 5.16 minutes for posaconazole. Quantification range varied from 0.125 µg/ml to 16 µg/ml. CONCLUSION: The selectivity and chromatographic purity of the obtained signal, the detection limits, and the standardized quantification make this method an excellent tool for the therapeutic monitoring of patients treated with voriconazole.

Introducción. Hasta la fecha, Colombia no cuenta con un servicio especializado de medición de niveles séricos de antifúngicos, procedimiento esencial para el adecuado seguimiento del tratamiento de infecciones fúngicas invasoras. Objetivo. Estandarizar y validar un protocolo ­simple, sensible y específico­ basado en la aplicación de cromatografía líquida de alta eficiencia acoplada con un detector de arreglo de diodos para la cuantificación de los niveles séricos de voriconazol. Materiales y métodos. Se usó un equipo HPLC-Agilent™, serie-1200, con un detector UVDAD, una columna analítica Eclipse-XDB-C18 y una pre-columna Eclipse-XDB-C18, ambas de la marca Agilent. Como control primario se utilizó voriconazol y como control interno, posaconazol. La validación se hizo cumpliendo todos los criterios de aceptación recomendados por la Food and Drug Administration (FDA). Resultados. Las mejores condiciones cromatográficas se obtuvieron con los siguientes parámetros: temperatura de la columna de 25 °C, detección UV-VWD de 261 nm, volumen de inyección de 50 µl, flujo de 0,8 ml/minuto y un tiempo de corrido de 10 minutos. La fase móvil usada fue acetonitrilo:agua (60:40) y los tiempos finales de retención fueron de 3,13 para voriconazol y de 5,16 minutos para posaconazol. El rango de cuantificación fue desde 0,125 µg/ml hasta 16 µg/ml. Conclusiones. La selectividad y la pureza de la señal cromatográfica, así como los límites de detección y cuantificación estandarizados hacen de esta metodología una excelente herramienta para el seguimiento terapéutico de pacientes tratados con voriconazol o en profilaxis con este fármaco.

Development of an on-site therapeutic drug monitoring method using a portable spectrometer.

We report on the development of an on-site therapeutic drug monitoring (TDM) method for vancomycin (VCM) utilizing a portable spectrometer and commercially available immunoturbidimetric assay reagents designed for automated clinical chemistry analyzers. The method enables the quantification of VCM in plasma samples within 10 min, with a good correlation between the measured values and the theoretical values (r2 = 0.995). The intra and inter-day precisions were found to be below 12.5% and 17.7%, respectively. Moreover, we established a correlation between the quantitative values using this method and those measured through HPLC-UV and automated clinical chemistry analyzers, showing good reliability (R2 = 0.970 and 0.951, respectively). This method allows anyone to rapidly perform TDM at the bedside and is expected to be used to evaluate appropriate drug therapy.

Evaluation of Busulfan as a Third-Party Immunoassay on a Clinical Chemistry Analyzer.

BACKGROUND: Busulfan is widely used in conditioning regimens to prepare patients for hematopoietic stem cell transplantation. Therapeutic drug monitoring (TDM) is critical due to large inter- and intra-individual variability in busulfan pharmacokinetics, and the risk of adverse consequences of toxicity including hepatic veno-occlusive disease. Busulfan is most commonly measured by liquid chromatography-mass spectrometry (LC-MS/MS), which is not as widely available in clinical laboratories as automated routine clinical chemistry analyzers. The objective was to perform analytical verification of a busulfan immunoassay on the Abbott Alinity c platform. METHODS: The MyCare Oncology busulfan immunoassay was configured as a third-party reagent on the Abbott Alinity c. Imprecision, linearity, sample carryover, and onboard stability of reagent studies were evaluated. The performance of the busulfan immunoassay using the Abbott Alinity c was compared to the Beckman Coulter AU480 using sodium heparinized plasma, as well as to LC-MS/MS using lithium heparinized plasma. RESULTS: The imprecision goal of 8% was met, and linearity within the analytical measurement range of 240 to 1700 ng/mL was verified. Sample carryover was negligible, and the reagents were stable onboard for at least 84 days. The busulfan immunoassay correlated well with LC-MS/MS (slope = 0.949, y-intercept = -7.8 ng/mL, r2 = 0.9935) and the Beckman Coulter AU480 (slope = 1.090, y-intercept = -34.5 ng/mL, r2 = 0.9988). CONCLUSIONS: This study demonstrated successful analytical verification of a busulfan third-party immunoassay on the Abbott Alinity c platform. The ability to perform TDM of busulfan on a routine clinical chemistry analyzer will positively impact turnaround times to improve patient outcomes.

A retrospective analysis to estimate trough concentrations of teicoplanin in patients with suspected or documented Gram-positive infections

Abstract Teicoplanin is a glycopeptide antibiotic commonly used to treat Gram-positive bacterial infections in the clinic. The aim of this study was to provide a therapeutic reference for the clinical application and dosage regimen adjustment of teicoplanin by identifying factors associated with its plasma trough concentration (Ctrough). A retrospective study was performed on patients with suspected or documented Gram-positive infections who were hospitalized from November 2017 to January 2020 and treated with teicoplanin while undergoing routine therapeutic drug monitoring (TDM). A total of 112 Ctrough trough measurements were obtained from 72 patients were included in this study. SPSS software was used for correlation analysis and receiver operator characteristic curve (ROC) analysis. The Ctrough for teicoplanin showed statistically significant relationships (P<0.05) with PLT, Scr, CLcr, eGFR, BUN and Cys-C. ROC curve analysis revealed that CLcr and eGFR were more sensitive and specific for Ctrough compared to the other factors. These findings should be considered in the clinical application of teicoplanin and for its dosage adjustment.

Preliminary results using a kit to measure tamoxifen and metabolites concentrations in capillary blood samples from women with breast cancer.

The aim of the study was to compare 3 blood sampling methods, including capillary blood sampling, for determining Tamoxifen (TAM), Z-endoxifen (END), and 4-hydroxytamoxifen (4HT) concentrations. High performance liquid chromatography-mass spectrometry was used to quantify concentrations of TAM, END, and 4HT in plasma, venous blood, and capillary blood samples of 16 participants on TAM therapy for breast cancer. The rhelise kit was used for capillary sampling. Calibration curves using 13C-labeled analogs of TAM, END, and 4HT as internal standards were used for quantifications. A capillary sampling kit was used successfully for all participants. Mean TAM concentrations did not differ significantly in the 3 types of samples. Mean END and 4HT concentrations did differ significantly between capillary and venous blood samples, possibly related to photodegradation in the internal standards prior to use or degradation products with chromatographic retention times similar to the metabolites. TAM, END, and 4HT concentrations were relatively stable when stored for 14 days at 8 °C and 20 °C. Therapeutic drug monitoring of TAM using an innovative kit and capillary blood sampling is feasible. Preliminary data from this study will aid in developing a multicenter, randomized clinical trial of personalized TAM dose monitoring and adjustments, with the goal of enhancing the quality-of-life and outcomes of patients with breast cancer.Clinical Trial Identification: EudraCT No 2017-000641-44.

Evaluation of BD Barricor™ and PST™ blood collection tubes compared to serum for testing 11 therapeutic drugs on a Roche Cobas® 8000 platform.

INTRODUCTION: The type of blood collection tube used when obtaining samples for therapeutic drug monitoring (TDM) has important implications on the accuracy of results. Serum tubes without a gel separator are currently considered best practice. We sought to evaluate the performance of Barricor™, a novel plasma tube that utilizes an inert mechanical separator, as well as a gel-based tube (PST™) for testing acetaminophen, digoxin, gentamicin, methotrexate, phenobarbital, phenytoin, salicylate, vancomycin, valproic acid, carbamazepine, and theophylline on a Roche Cobas® 8000 platform. METHODS: Paired patient samples were collected from individuals taking at least one of the medications evaluated. These were supplemented with spiked specimens to ensure a minimum of 40 paired samples per drug. All drugs were measured within two hours of collection on Roche e602 or c502 instruments. Deming regression was used to assess bias between Barricor™ vs serum and PST™ vs serum. Seven-day refrigerated stability was also assessed in Barricor™, PST™, and serum tubes in a subset of samples (n = 10) for each drug. RESULTS: Drug concentrations in Barricor™ were similar to serum for each drug assessed. In contrast, a negative bias was observed in PST™ compared to serum tubes for carbamazepine (-7.6%) and phenytoin (-6.8%) although this did not surpass our total allowable error goal of 10%. All drugs recovered within ±10% of baseline value when samples were stored refrigerated for 7 days except for carbamazepine, phenytoin, and phenobarbital where significant analyte loss was observed within the first day in PST™ tubes. CONCLUSION: Barricor™ tubes are a suitable alternative to serum for TDM on the Roche Cobas® 8000 platform.

Therapeutic drug monitoring of gabapentin: the applicability in patients with neuropathic pain

Abstract Gabapentin is an antiepileptic drug prescribed for several neuropathic pain conditions. This study aimed to evaluate gabapentin (GAB) trough plasma concentration range and the applicability of therapeutic drug monitoring in patients with neuropathic pain. Fifty-three patients with neuropathic pain, aged 20 to 75, received gabapentin as treatment for at least 7 days. Gabapentin plasma concentration was sampled before GAB administration and quantified by liquid chromatography with a UV detector. GAB trough plasma concentration ranged between 0.40 and 11.94 µg/mL in patients with chronic neuropathic pain. No differences were observed in terms of GAB plasma concentrations between responsive and non-responsive patients. Our data suggest that the reference ranges suggested in the literature for patients with epilepsy should not be used for patients with neuropathic pain. Therapeutic drug monitoring of GAB was shown to be an important tool to assess treatment adherence.

LC-MS/MS method for simultaneous quantification of the first-line anti-tuberculosis drugs and six primary metabolites in patient plasma: Implications for therapeutic drug monitoring.

The pharmacokinetic profiling of drug substances and corresponding metabolites in the biological matrix is one of the most informative tools for the treatment efficacy assessment. Therefore, to satisfy the need for comprehensive monitoring of anti-tuberculosis drugs in human plasma, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous quantification of first-line anti-tuberculosis drugs (ethambutol, isoniazid, pyrazinamide, and rifampicin) along with their six primary metabolites. Simple single-step protein precipitation with methanol was chosen as the most convenient sample pre-treatment method. Chromatographic separation of the ten analyte mixture was achieved within 10 minutes on a reverse-phase C8 column using mobile phase gradient mode. The multiple reaction monitoring mode (MRM) was used for analyte detection and quantification in patient samples. The chosen quantification ranges fully covered expected plasma concentrations. The method exhibited acceptable selectivity; the within- and between-run accuracy ranged from 87.2 to 113.6%, but within- and between-run precision was between 1.6 and 14.9% (at the LLOQ level CV < 20%). Although the response of the isonicotinic acid varied depending on the matrix source (CV 21.8%), validation results proved that such inconsistency does not affect the accuracy and precision of results. If stored at room temperature plasma samples should be processed within 4 h after collection, temporary storage at -20 °C up to 24 h is acceptable due to stability issues of analytes. The developed method was applied for the patient sample analysis (n = 34) receiving anti-tuberculosis treatment with the first-line drugs.

An automated streamlined method for the therapeutic drug monitoring of digoxin based on the online-solid-phase extraction liquid chromatography tandem high-resolution mass spectrometry.

RATIONALE: Digoxin is widely used in the clinical treatment of cardiovascular diseases. However, due to its extremely narrow therapeutic window, therapeutic drug monitoring (TDM) is vitally important. In consideration of the time-consuming and labor-intensive nature of the traditional techniques, an automated and efficient method was required for the clinical individualized TDM of digoxin. METHODS: An online solid-phase extraction liquid chromatography tandem high-resolution mass spectrometry (online-SPE-LC-HRMS) method was developed and applied for the determination of digoxin in plasma. The online SPE-LC steps included pretreatment and separation of plasma samples that were carried out using a Waters Oasis HLB cartridge and XBridge Shield RP18 column, respectively. A high-resolution Q Orbitrap mass spectrometer with targeted-selected ion monitoring in negative scan mode was applied to monitor formate-adduct ions [M + HCOO]- m/z 825.42781 for digoxin. RESULTS: Linearity was shown over the range 0.1-10 ng mL-1 for digoxin with correlation coefficients of R2 > 0.999. The lower limit of quantitation (LLOQ) for digoxin was 0.1 ng mL-1 . Extraction recoveries ranged from 82.61% to 94.28% for digoxin. The intra- and inter-day precision values were < 5.53% with accuracy ranging from 84.97% to 96.75%. The total running time was 10 min for each sample. CONCLUSION: The established method displayed satisfactory recoveries, accuracy, precision, and stability, and successfully applied on the TDM of digoxin. This automated streamlined method provides a powerful tool to guide the individualized administration of digoxin, which is significant for the practice of precision medicine.

Viability of a Serum Infliximab Concentration-Detecting Reagent as a Qualitative Assay for an Infliximab Biosimilar.

The efficacy of infliximab in treating rheumatoid arthritis depends on its serum trough concentration, which must be maintained at a minimum of 1 µg/mL to achieve the desired effects. However, Japan's National Health Insurance system does not cover tests for rheumatoid arthritis patients undergoing treatment with biosimilar infliximab because its performance as a biosimilar remains unclear. This study aimed to investigate whether the Remi-check Q qualitative assay yields comparable results for biosimilar infliximab and the originator product. Infliximab BS 100 "NK" and Remicade 100® were separately diluted in pooled human serum to yield test samples at the following concentrations: 0.30, 0.70, 1.20, and 3.00 µg/mL. Prepared samples were quantitatively assessed using an enzyme-linked immunosorbent assay (ELISA) and qualitatively using Remi-check Q, and the results obtained for the originator and biosimilar product were compared. For both originator and biosimilar infliximab, Remi-check Q yielded a negative result for all 0.30 and 0.70 µg/mL samples and a positive result for all 3.00 µg/mL samples. However, negative results were obtained with a fraction of the 1.20 µg/mL samples (biosimilar, 4/15; originator, 3/15). Concurrence rates between the results of quantitative ELISA and qualitative Remi-check Q analyses were comparable between originator and biosimilar infliximab at all tested concentrations. These results indicate that Remi-check Q yields comparable results for biosimilar infliximab and the originator product on being used as a qualitative assay for trough serum levels.

Use of an electronic medication monitoring device to estimate medication adherence in kidney transplant patients.

Electronic medication monitoring devices (EMD) have been used as a gold standard for assessing medication adherence. We used a wireless EMD (SimpleMed+), assessed its usability in patients after kidney transplantation (KTx), evaluated adherence, and analyzed concordance with other adherence measures. Fifty-five patients (53% female, mean age 46 years) at least 6 months after KTx agreed to use the EMD over a period of 8 weeks. Self-reported adherence was measured with the BAASIS, and immunosuppressant trough level variability was assessed prior to and again during the study period. Fourteen patients stopped using the EMD or were low users (<70%). These non-completers reported that using the EMD would interfere with their daily activities. Taking-adherence of the completers was high with 98.3% (±1.9) over the entire study period. Timing-adherence was somewhat lower (94.6% ± 7.9) and decreased during the second half of the study. We found statistically significant correlations between EMD results and self-reported adherence with moderate effect sizes, but no significant association with trough level variability. The low usage of the EMD supports the need to assess the practicability of an EMD before applying it in research and clinical routine. Taking- and timing-adherence of KTx patients using the EMD was satisfactory. Self-reported adherence might be a good enough estimate of medication adherence.

Sensor-Based Electronic Monitoring for Asthma: A Randomized Controlled Trial.

BACKGROUND: Although sensor-based monitoring of daily inhaled corticosteroids (ICSs) and short-acting ß-agonist medications may improve asthma outcomes, the effectiveness of these interventions in diverse pediatric populations remains unclear. METHODS: Caregiver and child dyads were randomly assigned to receive inhaler sensors that allowed for caregiver and clinician electronic monitoring of medications. End points included Asthma Control Test scores (≥19 indicated asthma control) and asthma health care use. Caregiver quality of life (QoL) and child ICS adherence were also assessed. Multilevel models were used to estimate adjusted changes from baseline. RESULTS: Dyads were assigned to the control (n = 127) or intervention (n = 125) arms. At the end line, the mean Asthma Control Test score increased from 19.1 (SE = 0.3) to 21.8 (SE = 0.4) among the intervention and from 19.4 (SE = 0.3) to 19.9 (SE = 0.4) among the control (Δintervention-control = 2.2; SE = 0.6; P < .01). Adjusted rates of emergency department visits and hospitalizations among the intervention were significantly greater (incidence rate ratioemergency department = 2.2; SE = 0.5; P < .01; incidence rate ratiohospital = 3.4; SE = 1.4; P < .01) at endline than the control. Caregiver QoL was greater among the intervention at the endline (Δintervention-control = 0.3; SE = 0.2; P = .1) than the control. CONCLUSIONS: Findings suggest that sensor-based inhaler monitoring with clinical feedback may improve asthma control and caregiver QoL within diverse populations. Higher health care use was observed among the intervention participants relative to the control, indicating further refinement is warranted.

A Wearable Surface-Enhanced Raman Scattering Sensor for Label-Free Molecular Detection.

A wearable surface-enhanced Raman scattering (SERS) sensor has been developed as a patch type to utilize as a molecular sweat sensor. Here, the SERS patch sensor is designed to comprise a sweat-absorbing layer, which is an interface to the human skin, an SERS active layer, and a dermal protecting layer that prevents damage and contaminations. A silk fibroin protein film (SFF) is a basement layer that absorbs aqueous solutions and filtrates molecules larger than the nanopores created in the ß-sheet matrix of the SFF. On the SFF layer, a plasmonic silver nanowire (AgNW) layer is formed to enhance the Raman signal of the molecules that penetrated through the SERS patch in a label-free method. A transparent dermal protecting layer (DP) allows laser penetration to the AgNW layer enabling Raman measurement through the SERS patch without its detachment from the surface. The molecular detection capability and time-dependent absorption properties of the SERS patch are investigated, and then, the feasibility of its use as a wearable drug detection sweat sensor is demonstrated using 2-fluoro-methamphetamine (2-FMA) on the human cadaver skin. It is believed that the developed SERS patch can be utilized as various flexible and wearable biosensors for healthcare monitoring.

Application of Potentiometric Sensors in Real Samples.

Potentiometry is one of the most important electrochemical methods and potentiometric based sensors have been extensively studied by researchers for many years. The fact that potentiometric sensors have several advantages over other analytical devices is another reason for intensive research on the topic. In this area, hundreds of different sensors have been developed till today and introduced into the literature. The successful use of the developed sensors, particularly in real sample analysis, has made potentiometric sensors the center of attention. In this review, we highlight the studies which have been successfully applied to the developed drug samples and also to many real samples, with high recovery rates.

A Review of Different Analytical Techniques for Fexofenadine Hydrochloride and Montelukast Sodium in Different Matrices.

Fexofenadine hydrochloride is an antihistamine agent used for the treatment of allergic disorders like rhinitis. It is a second generation antihistamine. Montelukast sodium is an anti-asthmatic agent and leukotriene receptor antagonist used in the treatment of respiratory disorders. This article exemplifies the reported analytical methods like electrometric methods, ultraviolet spectroscopy, mass spectroscopy, thin layer chromatography, high performance liquid chromatography, high performance thin layer chromatography and tandem spectroscopy for determination of fexofenadine HCl and montelukast sodium in dosage form and in biological matrices. This review covers almost all the analytical methods for fexofenadine hydrochloride and montelukast sodium form 1968-2018 years. Complete analytical validation parameters reported are discussed in this review for both analytes. Among various analytical methods, HPLC and UV-visible spectrophotometry were found to be the most extensively used methods by the researchers.

Analytical Methods for Determination of Apremilast from Bulk, Dosage Form and Biological Fluids: A Critical Review.

Apremilast is an anti-inflammatory agent. It has been a flourishing molecule in the field of dermatology. In the year 2014, Apremilast got its approval for treatment of psoriatic arthritis. Presently it is known to treat a number of other conditions, including atopic dermatitis and plaque psoriasis. Apremilast a phthalimide derivative, is non-hygroscopic in nature. It is practically insoluble in water. Apremilast acts by inhibiting the activity of phosphodiesterase 4 (PDE4), an intracellular enzyme. Analytical method plays a key role to understand the physio-chemical properties of a drug molecule. Because of poor solubility and low permeability, analytical method development and formulation becomes challenging. Till date, there are no standard test methods available to analyze Apremilast. So, a critical review of the analytical techniques of Apremilast was carried out. The literature search was done by screening the papers reporting analytical techniques of Apremilast from year 2014 to 2019. Methodologies particularly UV spectroscopy, HPTLC, HPLC, X-ray diffraction, NMR, LC-MS were collected and reviewed. Interminable efforts are made by the researchers to develop simple, accurate, robust and cost-effective methods of analysis. In pharmaceutical research, this information will aid in the development of new delivery systems. The review will prove beneficial and advantageous pre-formulation studies and will guide the formulation development.

Monitoring DOACs with a Novel Dielectric Microsensor: A Clinical Study.

BACKGROUND: There are acute settings where assessing the anticoagulant effect of direct oral anticoagulants (DOACs) can be useful. Due to variability among routine coagulation tests, there is an unmet need for an assay that detects DOAC effects within minutes in the laboratory or at the point of care. METHODS: We developed a novel dielectric microsensor, termed ClotChip, and previously showed that the time to reach peak permittivity (T peak) is a sensitive parameter of coagulation function. We conducted a prospective, single-center, pilot study to determine its clinical utility at detecting DOAC anticoagulant effects in whole blood. RESULTS: We accrued 154 individuals: 50 healthy volunteers, 49 rivaroxaban patients, 47 apixaban, and 8 dabigatran patients. Blood samples underwent ClotChip measurements and plasma coagulation tests. Control mean T peak was 428 seconds (95% confidence interval [CI]: 401-455 seconds). For rivaroxaban, mean T peak was 592 seconds (95% CI: 550-634 seconds). A receiver operating characteristic curve showed that the area under the curve (AUC) predicting rivaroxaban using T peak was 0.83 (95% CI: 0.75-0.91, p < 0.01). For apixaban, mean T peak was 594 seconds (95% CI: 548-639 seconds); AUC was 0.82 (95% CI: 0.73-0.91, p < 0.01). For dabigatran, mean T peak was 894 seconds (95% CI: 701-1,086 seconds); AUC was 1 (p < 0.01). Specificity for all DOACs was 88%; sensitivity ranged from 72 to 100%. CONCLUSION: This diagnostic study using samples from "real-world" DOAC patients supports that ClotChip exhibits high sensitivity at detecting DOAC anticoagulant effects in a disposable portable platform, using a miniscule amount of whole blood (<10 µL).

An Investigative Review for Pharmaceutical Analysis of 1,4-Dihydropyridine-3,5-Dicarboxylic Acid Derivative: Cilnidipine.

Hypertension is commonly a quiet condition, and it expands the risk of heart diseases and stroke. Calcium delivers a substantial role in cardiovascular functions and hence is essential for cardiac automaticity and functioning. Calcium channel antagonists are the choice of drugs for the management of cardiovascular diseases; they precisely stop the introduction of calcium through L-type calcium channels are existing channels in the heart. Cilnidipine belongs to the class 4th generation calcium channel blockers as a foremost therapeutic agent used in the treatment of hypertension and heart diseases. This review article focuses on an inclusive account of crucial analytical methodologies used for the pharmaceutical analysis of cilnidipine in pure forms, biological samples and pharmaceuticals. According to literature reports several analytical techniques such as hyphenated techniques, high-performance thin-layer chromatography, high-performance liquid-chromatography, capillary electrophoresis, voltammetry, UV/Vis-spectrophotometry, and Fourier-transform infrared spectroscopy approaches have been used for determination of cilnidipine alone or in the combined dosage form. We have also discussed the pharmacopeial assay methods, physicochemical properties, and also depict the stacked column chart for year wise publication count for cilnidipine. From literature, concluded that the high-performance liquid-chromatography and UV/Vis-spectrophotometry methods are the most prevailing methods for the analysis of cilnidipine. The data presented in this review may provide a very significant base for further studies on cilnidipine in the area of drug analysis.