A new stability-indicating HPLC-UV method for determination of amlodipine besylate and its impurities in drug substance.

A new fast stability-indication high performance liquid chromatography method was developed and validated for the determination of amlodipine besylate and its organic impurities in drug substance. The separation of amlodipine and its seven impurities was achieved on a core shell C18 column, 100 mm × 4.6 mm; 2.6 µm, within 15 min. The mobile phase comprised of 0.4% ammonium hydroxide in water and methanol delivered in a gradient mode; the method detection wavelength is 237 nm. The selected column is stable at high pH and provided a good peak shape for basic compounds. Amlodipine besylate was subject to acid, base, oxidative, thermal, and photolytic stress conditions. The degradation products were well resolved from the amlodipine peak and its impurities. Major degradants were analyzed by liquid chromatography coupled with single-quadrupole mass detector. Amlodipine peak was shown to be free of co-elution by mass spectral analysis in all stress conditions. The method was validated in terms of specificity, linearity, accuracy, precision, and robustness. The developed method could be applied for routine quality control analysis of amlodipine besylate drug substance.

Development and validation of a stability indicating HPLC method for organic impurities of erythromycin stearate tablets.

A rapid, sensitive, and accurate high-performance liquid chromatography (HPLC) method was developed and validated for the separation and analysis of organic impurities in erythromycin stearate tablets. The method separates Erythromycin, Erythromycin B, Erythromycin C and nine impurities (EP Impurity A, B, C, D, E, F, H, I and M). The chromatographic separation was achieved on a Waters XBridge C18 (100 mm × 4.6 mm, 3.5 µm) column. The mobile phase comprised of 0.4 % ammonium hydroxide in water and methanol delivered in a gradient mode. The compounds of interest were monitored at 215 nm. The stability-indicating capability of this method was evaluated by performing stress studies. Erythromycin was found to degrade significantly under acid, base, and oxidative stress conditions and it was only stable under thermal and photolytic degradation conditions. The degradation products were well resolved from the erythromycin peaks. In addition, the major degradants formed under stress conditions were characterized by ultra-high-performance liquid chromatography coupled with Single-Quadrupole Mass Spectrometer (UHPLC-QDa). The method was validated to fulfill International Conference on Harmonization (ICH) requirements and this validation included specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, and robustness. The developed method could be incorporated into the USP monograph and applied for routine quality control analysis of erythromycin stearate tablets.

Cancer vaccine adjuvants--recent clinical progress and future perspectives.

Despite recent breakthroughs in the prognosis, prevention and treatment, cancer still remains the leading cause of death and affects millions of people worldwide. With the US FDA approval of various preventive cancer vaccines such as Gardasil (Merck), Cervarix (Glaxosmithkline) and the therapeutic vaccine Sipulencel-T (Provenge), cancer vaccine development is gaining huge ground. Approval of these vaccines has encouraged the concept of cancer treatment through cellular immunotherapy. The FDA approval of the above vaccines has provided support for renewed interest and attention which the development of new therapeutic cancer vaccines deserves. However, most of the new generation vaccines including that for cancer are poorly immunogenic sub-unit vaccines and thus essentially need adjuvants in their formulations to compensate for the immune suppression. Adjuvants are the essential components of a potent vaccine which increases the efficacy by enhancing the antigen-specific immune response. However, the design of a successful adjuvant is not easy because of the complexity and the difficulty in designing adjuvants that are safe, potent and economically viable. The present communication takes a short review of the advancements in adjuvant technology, current clinical scenario of new adjuvants and application of their molecularly defined formulations to new generation cancer vaccines which are currently under development.

Steroidal pyrazolines and pyrazoles as potential 5α-reductase inhibitors: synthesis and biological evaluation.

Taking pregnenolone as the starting material, two series of pyrazolinyl and pyrazolyl pregnenolones were synthesized through different routes. The synthesis of the analogs of both series is multistep and proceeds in good overall yields. While the key step in the synthesis of pyrazolinyl pregnenolones is the heterocyclization of benzylidine derivatives (3) in presence of hydrazine hydrate, it is the condensation of 3ß-hydroxy-21-hydroxymethylidenepregn-5-en-3ß-ol-20-one (5) with phenylhydrazine in the synthesis of pyrazolyl derivatives. Compounds of both the series were tested for their 5α-reductase inhibitory activities. Amongst all the compounds screened for their 5α-reductase inhibitory activities, compound 4b, 4c and 6b were found to be the most active.

New triterpenoids from Arisaema jacquemontii.

Phytochemical investigation of the roots of Arisaema jacquemontii led to the isolation of two new triterpenoids, which were characterized by NMR, IR, and MS spectra as 30-nor-lanost-5-ene-3beta-ol (1) and 30-norlanost-5-ene-3-one (2).