A novel method for the quantification of anlotinib in human plasma using two‐dimensional liquid chromatography

Abstract

A simple, efficient, and stable detection method of two-dimensional liquid chromatography (2D-LC) was established and validated to determine anlotinib in the human plasma. The 2D-LC system comprises a first-dimensional column (LC1), an intermediate transfer column, and a second-dimensional column (LC2). With simple protein precipitation treatment, the samples were processed directly for detection. The analysis cycle time was completed within 9.50 min. For the anlotinib concentrations, the calibration curve was linear over the 5.00-320.00 ng/mL range. The intra-day and inter-day precision ranges were 0.77-6.22% and 1.92-4.26%, respectively, for anlotinib concentrations. The recoveries were in the range of 97.85-102.50%. A total of 135 plasma samples from 94 patients were analyzed by our method. The plasma concentrations of patients were in the range of 5.17-106.38 ng/mL, in which the female had a higher plasma concentration (6.44-106.38 ng/mL). The simultaneous application of dexamethasone can increase the anlotinib concentration in the plasma.In our clinical application, we found that the factors that affect the plasma concentration include the time and dose of the medication, gender, and drug interactions. The method appears to be sensitive, precise, selective, and suitable for determining the concentration of anlotinib in the plasma sample.

Establishment and validation of a LC–MS/MS method for the determination of anlotinib in human plasma: Application to therapeutic drug monitoring

“…The clinical results showed that in the 10 mg dose of TC patients, the mean peak concentration of anlotinib in women was 109.5 ng·ml −1 , which was much higher than the value of 73.5 ng·ml −1 in men. This also confirms the conclusion of Li et al (2021) that under the same treatment conditions, the plasma concentration of female patients is higher than that of male patients. At the same time, we also found that at a dose of 12 mg in all female patients, the average blood concentration of TC patients was 118.8 ng·ml −1 , which was much higher than that of BC patients at 87.1 ng·ml −1 .…”

“…The clinical results showed that in the 10 mg dose of TC patients, the mean peak concentration of anlotinib in women was 109.5 ngÁml À1 , which was much higher than the value of 73.5 ngÁml À1 in men. This also confirms the conclusion of Li et al (2021) that under the same treatment conditions, the plasma concentration of female patients is higher than that of male patients.…”

“…To date, several methods have been used to detect the concentration of anlotinib. These methods include high‐performance liquid chromatography–mass spectrometry (LC–MS/MS) to determine the concentration of antlotinib in mouse plasma (Du et al, 2019; Wang et al, 2019) and two‐dimensional liquid chromatography (2D‐LC) to determine the concentration of anlotinib in human plasma (Li et al, 2021). Zhou et al reported an LC–MS/MS method for the simultaneous determination of 12 TKIS in human plasma (Zhou et al, 2021).…”

Association between anlotinib trough plasma concentration and treatment outcomes in advanced non-small-cell lung cancer

“…ANL is mainly metabolized by CYP1A2 and CYP3A4/5 and secondary metabolic enzymes including CYP2C9, CYP2C19 and CYP2D6 (12, 13). Dexamethasone is a moderate inducer of CYP3A, which could accelerate the metabolism of ANL and reduce exposure (14). CYP2C19 rs3814637 and rs11568732 gene polymorphisms may also influence the ANL exposure (15).…”

“…CYP2C19 rs3814637 and rs11568732 gene polymorphisms may also influence the ANL exposure (15). In addition, Li et al and Yu et al has been reported that ANL plasma concentration is higher in female patients than male patients under the same dose (14,16). Beside these known contributions to variability in ANL exposure, patient characteristics such as age, body mass index, renal function and liver function may also contribute to variability in ANL exposure.…”