A Simple HPLC-UV Method for Ivosidenib Determination in Human Plasma.

Ivosidenib is used for the treatment of acute myeloid leukemia (AML) with isocitrate dehydrogenase 1 (IDH1) mutations. However, increased blood concentrations of ivosidenib are associated with a risk of a prolonged QT interval in patients with AML. Therapeutic drug monitoring in patients with AML with IDH1 mutation offers the potential to improve treatment efficacy while minimizing toxicity. In this study, we developed an efficient high-performance liquid chromatography-ultraviolet (HPLC-UV) method for the quantification of ivosidenib in plasma. Human plasma samples (50 µL) were processed by protein precipitation using acetonitrile, followed by chromatographic separation on a reversed-phase column with an isocratic mobile phase of 0.5% KH2PO4 (pH 4.5) and acetonitrile (45:55, v/v) at a flow rate of 1.0 mL/min, with ultraviolet detection at 245 nm. Calibration curves were linear over the range of 0.25-20 µg/mL with a coefficient of determination (r2) of 0.99999. Intra-day and inter-day precision were 1.20-8.04% and 0.69-4.20%, respectively. The assay accuracy was -2.00% to 1.93% and recovery was >91.2%. These findings support the effectiveness of the newly developed HPLC-UV method for the quantification of ivosidenib in human plasma. This simple and cost-effective method is expected to expand ivosidenib monitoring in laboratories lacking LC-MS/MS instruments.

Development of a simple high-performance liquid chromatography-ultraviolet method for sotorasib quantification in human plasma: Implications for therapeutic drug monitoring.

Sotorasib, an oral small-molecule inhibitor, reportedly exerts promising activity against Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant tumors. However, the currently administered dose may fail to represent the optimal dose based on the therapeutic efficacy. Herein, we developed a simple and sensitive method using high-performance liquid chromatography with ultraviolet (HPLC-UV) to measure the sotorasib concentration in human plasma. The sotorasib calibration curve exhibited linearity across the concentration range of 0.10-20.0 µg/mL (r2 = 0.9999). The coefficients of intra- and inter-day validation ranged between 0.79-9.75% and 3.01-6.13%, respectively. The assay accuracy ranged between -3.14 and 5.18%, with > 98.5% recovery. Subsequently, we applied the developed method to estimate sotorasib concentrations in a patient with KRAS G12C-mutated non-small cell lung cancer. We anticipate that our HPLC-UV method will be valuable for assessing the safety and efficacy of sotorasib in larger patient cohorts.

Plasma Cabozantinib Level Measurement in Patients with Renal Cell and Hepatocellular Carcinomas Using a Simple HPLC-UV Method Suitable for Clinical Application.

Cabozantinib, which is used to treat renal cell and hepatocellular carcinomas, is often associated with dose-dependent adverse events. Monitoring the levels of cabozantinib in the blood may maximize the therapeutic effect and prevent serious adverse events. In this study, we developed a high-performance liquid chromatography-ultraviolet (HPLC-UV) method of measuring plasma cabozantinib concentration. Human plasma samples (50 µL) were processed by simple deproteinization with acetonitrile, followed by chromatographic separation on a reversed-phase column with an isocratic mobile phase of 0.5% KH2PO4 (pH 4.5) and acetonitrile (43:57, v/v) at a flow rate of 1.0 mL/min, with a 250 nm ultraviolet detector. The calibration curve was linear over the concentration range (0.05-5 µg/mL) with a coefficient of determination of 0.99999. The accuracy of the assay ranged from -4.35% to 0.98%, and recovery was >96.04%. The measurement time was 9 min. These findings confirm the effectiveness of this HPLC-UV method for cabozantinib quantification in human plasma, which is sufficiently simple for use for monitoring patients in clinical settings.

Determination of Venetoclax Concentration in Plasma Using High-Performance Liquid Chromatography.

Venetoclax is an oral B-cell lymphoma-2 protein inhibitor. It is a key drug for the treatment of chronic lymphocytic leukemia and acute myeloid leukemia. However, venetoclax is administered at a fixed dose, irrespective of body surface area or weight. Furthermore, the plasma concentration of venetoclax varies widely between individuals and is influenced by diet. Therefore, individualized dosing using therapeutic drug monitoring (TDM) may help to optimize treatment in clinical practice. In this study, we aimed to develop a simple method to determine venetoclax concentrations in plasma. The analysis required the extraction of a 50-µL plasma sample and precipitation of proteins using acetonitrile extraction. Venetoclax and the internal standard (12.5-µg/mL ibrutinib) were separated by high-performance liquid chromatography (HPLC). The calibration curve was linear over the plasma venetoclax concentration range 0.25-10 µg/mL with a coefficient of determination (r2) of 0.9999. The coefficients of intra-day and inter-day validation were 0.8-4.1% and 1.3-3.3%, respectively. The assay accuracy was -2.8 to 1.6%, and the recovery was >97.2%. These results demonstrate a very simple, novel and sensitive HPLC-UV-based method for determining the concentration of plasma venetoclax, and confirm its applicability to the TDM of venetoclax in a clinical setting.

High-Performance Liquid Chromatography for Ultra-Simple Determination of Plasma Voriconazole Concentration.

Voriconazole is an antifungal drug used to treat invasive aspergillosis. Voriconazole exhibits nonlinear behavior and considerable individual variability in its pharmacokinetic profile. Invasive aspergillosis has a poor prognosis, and failure of treatment owing to low voriconazole blood levels is undesirable. Thus, therapeutic drug monitoring (TDM) of voriconazole is recommended. However, plasma voriconazole concentration is rarely measured in hospitals, and the TDM of voriconazole is not widely practiced in Japan. We aimed to develop an ultra-simple method to measure plasma voriconazole concentration. Ten microliters of plasma sample was extracted, and proteins were precipitated using methanol extraction. Voriconazole and ketoconazole (internal standard) were separated using high-performance liquid chromatography. A calibration curve was prepared, which was linear over plasma voriconazole concentrations of 0.125−12.5 µg/mL, with a coefficient of determination of 0.9999. The intra-day and inter-day validation coefficients were 0.9−2.2% and 1.3−6.1%, respectively. The assay accuracy was −4.2% to 1.6%, and recovery was >97.8%. Our ultra-simple, sensitive, and inexpensive high-performance liquid chromatography ultraviolet method to determine plasma voriconazole concentration will help improve the voriconazole TDM implementation rate and contribute to effective and safe voriconazole use.