New and sensitive HPLC-UV method for concomitant quantification of a combination of antifilariasis drugs in rat plasma and organs after simultaneous oral administration

• Published in: Analytical methods 2021-02, Vol.13 (7), p.933-945
• Main Authors: Permana, Andi Dian, Wahyudin, Elly, Ismail, Amir, Muh. Nur, Raihan, Muh, Anjani, Qonita Kurnia, Utomo, Emilia, Layadi, Patricia, Donnelly, Ryan F
• Format: Article
• Language: English
• Subjects: Acetonitrile; Administration, Oral; Albendazole; Animals; Biological properties; Biological samples; Calibration; Chromatography, High Pressure Liquid; Doxycycline; Drugs; Filariasis; High performance liquid chromatography; Humans; Ivermectin; Liquid chromatography; Metabolites; Oral administration; Pharmaceutical Preparations; Pharmacokinetics; Pharmacology; Prospective Studies; Rats; Rats, Wistar; Regulatory agencies; Stationary phase; Tissue Distribution; Toxicology; United States; Vector-borne diseases
• ISSN: 1759-9660; 1759-9679
• DOI: 10.1039/d0ay02258f

A combination treatment comprising ivermectin (IVM), albendazole (ABZ) and doxycycline (DOX) is often prescribed for lymphatic filariasis patients. Nevertheless, there has not been an analytical method established and documented to determine these compounds simultaneously. Herein, we report a new high-performance liquid chromatographic method coupled with a UV detector (HPLC-UV) to quantify these drugs in plasma and organs. This developed analytical method was validated according to the International Conference on Harmonization (ICH) and US Food and Drug Administration (FDA) guidelines. The validated method was successfully employed to analyze IVM, ABZ along with its metabolites (albendazole sulfoxide (ABZ-OX) and albendazole sulfone (ABZ-ON)), and DOX in the plasma and organs of Wistar rats after simultaneous oral administration. An Xselect CSH™ C 18 HPLC column was utilized as a stationary phase, with a mobile phase consisting of 0.1% v/v trifluoracetic acid in water and acetonitrile with a run time of 20 min. The calibration curves in biological samples were found to be linear across the concentration range of 0.01-5 μg mL −1 for IVM, ABZ and ABZ metabolites, and 0.025-10 μg mL −1 for DOX with an R value ≥0.998 in each case. The validated method was found to be selective, precise and accurate. Finally, the method developed in this study was deployed to assess the pharmacokinetic profiles and biodistribution of the combination of drugs after oral administration to Wistar rats. The validated HPLC-UV method in this study provides an extensive range of prospective applications for pharmacokinetic-based studies, therapeutic drug monitoring and toxicology. A sensitive HPLC-UV method for simultaneous analysis of the drugs used in lymphatic filariasis treatment, namely IVM, ABZ and DOX has been validated. The method was applied in pharmacokinetic and biodistribution studies in Wistar rats.