Development and validation of a stability-indicating RP-HPLC method for determination of atomoxetine hydrochloride in tablets.

This paper describes the development of a stability-indicating RP-HPLC method for the determination of atomoxetine hydrochloride (ATX) in the presence of its degradation products generated from forced decomposition studies. The drug substance was subjected to stress conditions of acid, base, oxidation, wet heat, dry heat, and photodegradation. In stability tests, the drug was susceptible to acid, base, oxidation, and dry and wet heat degradation. It was found to be stable under the photolytic conditions tested. The drug was successfully separated from the degradation products formed under stress conditions on a Phenomenex C18 column (250 x 4.6 mm id, 5 microm particle size) by using acetonitrile-methanol-0.032 M ammonium acetate (55 + 05 + 40, v/v/v) as the mobile phase at 1.0 mL/min and 40 degrees C. Photodiode array detection at 275 nm was used for quantitation after RP-HPLC over the concentration range of 0.5-5 microg/mL with a mean recovery of 100.8 +/- 0.4% for ATX. Statistical analysis demonstrated that the method is repeatable, specific, and accurate for the estimation of ATX. Because the method effectively separates the drug from its degradation products, it can be used as a stability-indicating method.

Simultaneous determination of imipramine hydrochloride and chlordiazepoxide in pharmaceutical preparations by spectrophotometric, RP-HPLC, and HPTLC methods.

A binary mixture of imipramine HCl and chlordiazepoxide was determined by three different methods. The first involved determination of imipramine HCl and chlordiazepoxide using the first derivative spectrophotometric technique at 219 and 231.5 nm over the concentration ranges of 1-20 and 2-24 microg/mL with mean accuracies of 99.47 +/- 0.78 and 101.43 +/- 1.20%, respectively. The second method utilized RP-HPLC with methanol-acetonitrile-0.065 M ammonium acetate buffer (45 + 25 + 30, v/v/v, pH adjusted to 5.6 +/- 0.02 with phosphoric acid) as the mobile phase pumped at a flow rate of 1.0 mL/min. Quantification was achieved using UV detection at 240 nm over concentration ranges of 0.25-4.0 and 0.1-1.6 microg/mL, with mean accuracies of 101.17 +/- 0.56 and 100.67 +/- 0.40% for imipramine HCl and chlordiazepoxide, respectively. The third method was HPTLC with carbon tetrachloride-acetone-triethylamine (pH 8.3; 6 + 3 + 0.3, v/v/v) as the mobile phase. Quantification was achieved with UV detection at 240 nm over concentration ranges of 50-600 and 20-240 ng/spot with mean accuracies of 99.51 +/- 0.59 and 100.59 +/- 0.84% for imipramine HCl and chlordiazepoxide, respectively. The suggested procedures were checked using prepared mixtures, and were successfully applied for the analysis of pharmaceutical preparations. The accuracy and precision of the methods were confirmed when the standard addition technique was applied. The results obtained by applying the proposed methods were statistically analyzed.

Development and validation of reversed-phase column high-performance liquid chromatographic and first-derivative UV spectrophotometric methods for estimation of voriconazole in oral suspension powder.

This research paper describes validated reversed-phase high-performance column liquid chromatographic (RP-HPLC) and first-derivative UV spectrophotometric methods for the estimation of voriconazole (VOR) in oral suspension powder. The RP-HPLC separation was achieved on Phenomenex C18 column (250 x 4.6 mm id, 5 microm particle size) using water-acetonitrile (40 + 60, v/v; pH adjusted to 4.5 +/- 0.02 with acetic acid) as the mobile phase at a flow rate of 1.4 mL/min and ambient temperature. Quantification was achieved with photodiode array detection at 255 nm over the concentration range of 0.1-1 microg/mL with mean recovery of 99.49 +/- 0.83% for VOR by the RP-HPLC method. Quantification was achieved with UV detection at 266 nm over the concentration range of 8-20 microg/mL with mean recovery of 99.74 +/- 0.664% for VOR by the first-derivative UV spectrophotometric method. These methods are simple, precise, and sensitive, and they are applicable for the determination of VOR in oral suspension powder.

Hydroxyl radical mediates the augmented angiotensin II responses in thoracic aorta of spontaneously hypertensive rats.

AIM: To investigate the role of hydroxyl radical in augmented angiotensin II (Ang II) responses in the thoracic aorta of spontaneously hypertensive rats (SHR). METHODS: To elucidate the role of hydroxyl radical, we used edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) as a tool for our study. The vascular responses to Ang II (10(-10) to 10(-6) mol/l), tert-butyl hydroperoxide (tBHP; 10(-6) to 10(-2) mol/l) and H(2)O(2) (10(-6) to 10(-2) mol/l) were constructed in aortic preparations obtained from control (WKY) and SHR in the absence and presence of edaravone. RESULTS: The vascular responses to Ang II, tBHP and H(2)O(2) were found to be enhanced in aortic preparations from SHR as compared to control WKY rats. Edaravone selectively attenuated the augmented responses to Ang II but not to tBHP and H(2)O(2) suggesting that the .OH radical is involved in the augmented responses to Ang II. The elevated blood pressure in SHR was restored to a near normal value after 2 weeks of edaravone (10 mg kg(-1) i.p., b.i.d.) treatment. CONCLUSION: From the results we infer that hydroxyl radical stress augments Ang II responses in the thoracic aorta of SHR and, by attenuating these enhanced vascular responses, edaravone could serve as an adjuvant antioxidant therapy for the vascular complications of hypertension.