Thermostability Testing and Degradation Profiles of Doxycycline in Bulk, Tablets, and Capsules by HPLC

摘要

A high-performance liquid chromatography (HPLC) method for the quantitation of doxycycline in bulk, tablets, and capsules after storage at –20, 5, 25, 40, 50, 60, and 70°C, has been developed and validated. The samples are eluted from a μ-Bondapak C8 column (4.6 ×× 150-mm, i.d., 5-μm particle size) at 27°C, with a mobile phase of acetonitrile–water–THF (29.5:70:0.5, v/v/v), adjusted to pH 2.5 with 1.0M HCl. The flow rate is 1.0 mL/min and detection by UV is at 350 nm. The stability of doxycycline in bulk and in pharmaceuticals is checked over 90 days. Doxycycline shows thermo-degradation after exposure to high temperature; tablets are more stable than capsules. The shelf lives (t90%) are determined to be 1.00, 2.84, and 5.26 years in bulk, capsules, and tablets, respectively, at 25°C. Metacycline and 6-epidoxycyline are identified as degradation products at high temperatures. Amounts of doxycycline, metacycline, and 6-epidoxycycline in all samples are determined by HPLC, and the results compare with those from micellar electrokinetic capillary chromatography. After 90 days, metacycline and 6-epidoxycyline are almost equal in test samples from standard bulk form, tablets, and capsules. It is 27.8 ± 0.3%, 13.7 ± 0.1%, and 18.8 ± 0.2%, respectively.