Rapid high pressure liquid chromatographic determination of amitriptyline hydrochloride in tablets and injectables: collaborative study.

A previously reported high pressure liquid chromatographic method for the determination of amitriptyline hydrochloride in dosage forms was modified to permit its use as a stability-indicating method. The modified method, entailing a nitrile bonded microparticulate column, a methanol-0.005M ammonium acetate (90 + 10) mobile phase, and photometric detection at 239 nm, was collaboratively tested by 10 laboratories. Each collaborator received samples of synthetic and commercial tablets and injections. The recovery from a synthetic injection at the 10.06 mg/mL spiking level averaged 98.6%. The amount of declared found in commercial injections averaged 103.1%. The pooled reproducibility SD (CV%) and repeatability SD (CV%) were +/- 2.12 (2.15) and +/- 1.81 (1.84), respectively. The recovery from synthetic tablet composite at the 7.45% spiking level averaged 102.0%. The amount of declared found for commercial 25 mg and 100 mg tablets averaged 96.7 and 97.9%, respectively. The pooled reproducibility SD (CV%) and repeatability SD (CV%) for these 3 tablet samples were +/- 1.89 (1.86) and +/- 1.66 (1.64), respectively. Content uniformity analysis of commercial 25 mg and 100 mg tablets (n = 10) gave amounts of declared values averaging 100.5% (range 92.4-108.8%) and 99.3% (range 89.6-107.0%), respectively. The pooled reproducibility SD (CV%) and repeatability SD (CV%) were +/- 3.23 (3.2) and +/- 2.78 (2.8), respectively. A commercial injectable preparation spiked with dibenzosuberone was also collaboratively analyzed by a thin layer method. The method was adopted interim official first action.