Identification of Novel Impurity of Ziprasidone.

Ziprasidone hydrochloride is a second-generation antipsychotic drug employed for the treatment of schizophrenia and acute mania or mixed episodes associated with bipolar disorder. During the scale-up of ziprasidone hydrochloride, an unknown impurity was observed in the batches ranging from 0.10% to 0.15% by HPLC-UV analysis. The structure of an unknown impurity was proposed as 3,3'-methylenebis(5-(2-(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)ethyl)-6-chloroindolin-2-one) which is named as methylene ziprasidone dimer (MZD impurity). It was isolated from an enriched sample by preparative HPLC, and its structure was elucidated by comprehensive analysis of HRMS, 1D NMR (1H, 13C), DEPT-135, 2D NMR (COSY, HSQC, HMBC) spectroscopy. A plausible mechanism for the formation of isolated impurity is proposed.

Beta-Alanine and Tris-(hydroxyl methyl) Aminomethane as Peak Modifiers in the Development of RP-HPLC Methods Using Aceclofenac and Haloperidol Hydrochloride as Exemplar Drugs.

In the present analytical approach, beta-alanine (ALA) and tris-(hydroxyl methyl) aminomethane (TRIS) were investigated as peak modifiers due to their water solubility and their possible peak modifying a property. These reagents were tested for their efficacy on the elution of aceclofenac (ACF) and haloperidol hydrochloride (HLC) from C18 column (250 mm × 4.6 mm, 5 µ) equipped with a photodiode array detector. The test reagents were investigated at 0.25 ± 0.05% concentration with a varying % aqueous composition on elution efficacy of HLC and ACF. The added ALA/TRIS in the mobile phase significantly (P < 0.05) improvised the symmetrical elution of HLC with 3-fold theoretical plates increase (P < 0.05) and 10-fold reduced capacity factor as compared to the control run. For ACF, the shoulder effect observed for ACF peak was eliminated. The optimized mobile phase was a combination of acetonitrile and water containing 0.25% beta-alanine/TRIS (pH 3.5 with ortho-phosphoric acid) at the ratio of 70:30 and 60:40% v/v, respectively, for ACF and HLC. The method was validated as per ICHQ2 guidelines. The column performance was tested for reproducibility in non-peak modifier applications and revealed a null effect on the column, thus these agents are relatively less toxic to HPLC columns.

Development of a sensitive bioanalytical method for the quantification of lacosamide in rat plasma. Application to preclinical pharmacokinetics studies in rats.

A sensitive and selective high performance liquid chromatographic (HPLC) method was developed and validated for quantification of lacosamide in rat plasma. A liquid-liquid extraction procedure was optimized to extract lacosamide from rat plasma. Chromatographic separation was accomplished using a reversed phase C18 Hichrom (250×4.6 mm, 5 µm) column with the mobile phase consisting of acetonitrile-phosphate buffer (pH 3.2±0.1; 20 mM) (21:79, v/v) at a flow rate of 1 mL/min. Both intra- and inter day assay precision and accuracy were lower than 15% CV. The lower limit of quantitation was 25 ng/mL for lacosamide and the response was linear in a concentration range from 25 to 10 000 ng/mL. The developed method was successfully used for the preclinical pharmacokinetic study of lacosamide in rats.

Spectrofluorimetric method for determination of citalopram in bulk and pharmaceutical dosage forms.

A simple accurate, sensitive reproducible spectrofluorimetric method was developed for the analysis of citalopram in pure and pharmaceutical dosage form. Citalopram showed strong native fluorescence in 0.05 M sulphuric acid having excitation at 239 nm and emission at 300 nm. All parameters like the effect of different solvents, pH, dilutions, reaction time, temperature and effect of excipients were thoroughly investigated. The calibration graph was linear in the range from 0.100 to 0.900 µg/ml. The proposed method was statistically validated and successfully applied for analysis of tablet dosage forms. The percentage recovery was found to be between 99.08% to 99.28%.