A rapid LC–MS/MS method for simultaneous determination of berberine and irbesartan in rat plasma: Application to the drug–drug pharmacokinetic interaction study after oral administration in rats

Abstract

A sensitive, reproducible, and specific liquid chromatography tandem mass spectrometry method was developed and validated to simultaneously determine the concentration of berberine (BBR) and irbesartan in Sprague–Dawley rat plasma, and applied to study the pharmacokinetic drug–drug interaction (DDI) between BBR and irbesartan in rats. In this method, diphenhydramine was used as the internal standard, and the liquid–liquid extraction method using ethyl acetate as the extraction agent was used for sample preparation. After extraction, the prepared samples were run on an Agilent Welchrom C18 column with the mobile phase consisting of methanol–acetonitrile–water solution with 0.5% formic acid (45:50:5, v/v/v) at a flow rate of 0.8 mL·min−1. The analytes BBR, irbesartan, and diphenhydramine (IS) were detected using multiple reactions monitoring mode, with the ion transitions being m/z 336.1 → m/z 320.0, m/z 429.1 → m/z 206.9, and m/z 256.2 → m/z 167.0, respectively. In the rats’ plasma, BBR had good linearity in the range of 0.5–100 ng·mL−1 with the lower limit of quantitation of 0.5 ng·mL−1, and the accuracy, intra‐day, and inter‐day precision were less than 12.33%. Irbesartan had good linearity in the range of 20–1200 ng·mL−1 with the lower limit of quantification of 20 ng·mL−1, and the accuracy, intra‐day, and inter‐day precision were less than 13.55%. The validated method was verified to meet the determination requirements of biological samples. It was the first time to study the pharmacokinetics of DDI between BBR and irbesartan successfully, which would be necessary and beneficial to explore the clinical safety and efficacy of the combination of BBR and irbesartan in the treatment of diabetic nephropathy.

Cardiovascular Effects of Herbal Products and Their Interaction with Antihypertensive Drugs—Comprehensive Review

“…When co-administered with irbesartan, as both are lipid-soluble and interact with CYP3A4 and P-gp, irbesartan enhances berberine’s bioavailability and absorption by inhibiting P-gp in the intestinal tract, extending its contact with CYP3A4, while berberine increases irbesartan’s concentration but has minimal influence on irbesartan metabolism. This co-administration elevates blood concentrations of both berberine and irbesartan compared to separate oral administrations [ 61 ].…”

Pharmacokinetic of berberine, the main constituent of Berberis vulgaris L.: A comprehensive review

“…The possible mechanism was that when irbesartan is at its highest concentration in the plasma, berberine is mainly removed from the plasma due to its poor solubility and bioavailability. The other possible mechanism could be that berberine showed a poor inhibition effect on P-gp (Zhou, Li, Sun, Li, & Liu, 2021).…”

LC method for the quantification of Quercetin, Berberine, and Phytosterol in lyophilized liposome

“…Various analytical techniques have been developed for the estimation of these compounds, either individually or in combination, from different sources. For instance, high-performance liquid chromatography (HPLC) and UFLC methods have been established for the estimation of Quercetin [16][17][18][19][20][21][22], whereas HPLC and HPTLC techniques have been used for the estimation of Berberine [23][24][25][26][27][28][29][30][31][32][33][34], alone or in combination. Similarly, HPLC methods have been utilized for the quantification of Phytosterols [35][36][37][38][39].…”