Patients with pemphigus vulgaris are prescribed an extemporaneously prepared antimicrobial mouthwash containing hydrocortisone, nystatin, diphenhydramine and tetracycline (HNDT) to prevent opportunistic infections. Literature shows that tetracycline has poorer aqueous stability compared to doxycycline. This study investigated how temperature and pH affect tetracycline stability in HNDT mouthwash and explored the feasibility of reformulating with doxycycline to attain a longer beyond-use date. The original and pH-modified tetracycline-formulated and doxycycline-formulated mouthwashes were stored at 5oC and 30oC for 7–21 days. The amounts of tetracycline or doxycycline remaining were quantified using a high-performance liquid chromatography (HPLC) method developed. The pH-modified mouthwashes generally showed lower stability than the original mouthwashes. Overall, doxycycline showed a better stability profile than tetracycline. The doxycycline-formulated mouthwash (without pH adjustment) was found to be most stable when stored at 5oC and enabled pemphigus patients to use the mouthwash for an extended period of 3–4 weeks