Elucidating the in vivo fate of pharmaceutical excipient sodium carboxymethylcellulose in rats using UHPLC- Q TRAP MS/MS and UHPLC- Q TOF MS/MS approach

Sodium carboxymethylcellulose acts as both a pharmaceutical excipient (interacting with drugs to affect metabolism) and an active substance (stimulating intestinal peristalsis via aqueous polymeric colloids). To clarify its in vivo fate and advance sodium carboxymethylcellulose-based adjuvant delivery, a targeted analysis was needed, using dextromethorphan hydrobromide as a model drug. A comprehensive LC-MS approach was established: UHPLC-Q TRAP MS/MS (quantitative) and HPLC-Q TOF MS/MS (qualitative) were used to study sodium carboxymethylcellulose pharmacokinetics, distribution, metabolism, and excretion in male Wistar rats, with/without co-administered dextromethorphan hydrobromide. The distribution of sodium carboxymethylcellulose is expedited to organs characterized by augmented blood flow velocities, including the spleen, liver, and heart. And about 66.4% sodium carboxymethyl cellulose was removed from plasma within 36 h. Results also showed that the excretion level of sodium carboxymethyl cellulose is less than the dosage administered, and almost all glycosidic bonds had been hydrolyzed in its process. The findings provide complete description of sodium carboxymethylcellulose in vivo fate, establishing a novel framework that facilitates the extensive utilization of this pharmaceutical excipient in the process of drug formulation development. Sodium carboxymethylcellulose (CMC-Na) is used in medicine for two main purposes. First, it works as a “pharmaceutical excipient” – this means it interacts with drugs and changes how drugs break down in the body. Second, it has its own active effect: it helps stimulate gut movement by forming a watery polymeric gel. But right now, we don’t fully understand what happens to CMC-Na once it’s inside the body. This lack of knowledge has held back its use in delivering drug adjuvants. So, we did a study to figure out CMC-Na’s journey in the body. We used a drug called dextromethorphan hydrobromide as a “model drug” (a standard drug to test with). For the study, we used two types of LC-MS technology – a tool that helps analyze substances in the body. One type (UHPLC-Q TRAP MS/MS) measured exactly how much CMC-Na was present. The other (HPLC-Q TOF MS/MS) identified what CMC-Na turned into. We tested male Wistar rats: some got only CMC-Na, while others got both CMC-Na and dextromethorphan hydrobromide. We then looked at how CMC-Na was absorbed, moved around the body, broken down, and removed from the rats. Our results showed that CMC-Na traveled faster to organs where blood flows more quickly – like the spleen, liver, and heart. Within 36 hours, about 66.4% of CMC-Na was cleared from the rats’ blood. We also found that less CMC-Na was removed from the body than the amount we gave. And almost all the “glycosidic bonds” (the chemical links holding CMC-Na together) were broken down during its journey in the body. This study gives us a full picture of what happens to CMC-Na inside the body. It also creates a new guide that will help make CMC-Na more widely used as a pharmaceutical excipient when developing new drug products.