Current Pharmaceutical Analysis - Volume 7, Issue 1, 2011

5-fluorouracil (5-FU or f5U) is a pyrimidine analogue, and is used as an antineoplastic drug. Working with antineoplastic drugs constitutes a health hazard for the people who handle them, mainly because of their mutagenicity, teratogenicity and carcinogenicity. This is the reason, why the determination of antineoplastic drugs in wipe samples obtained from the hospital departments, where antineoplastic drugs are prepared or administered is growing in importance. 5-fluorouracil has some unusual pharmacological characteristics, which make it suitable for therapeutic drug monitoring. Thus, its determination in plasma and other body fluids or in urine is important, too. Like other drugs, 5-fluorouracil is also determined in formulations during quality control or stability studies.

Acarbose is a clinically useful drug for the treatment of type II insulin-independent diabetes as a hypoglycemic agent. This minireview summarized detection and separation methods for the analysis and determination of anti-diabetes drug acarbose and its structural analogs, including HPLC, enzyme-based biosensor and capillary electrophoresis. Besides the protocol, principle behind each technique is presented together with its strengths and weaknesses. Finally, we analyze the future trends in the acarbose analysis.

A reverse phase liquid chromatographic analytical method was developed for the simultaneous determination of Dapivirine and DS003 content in tablet dosage form. The chromatographic separation was achieved by using a C18 column with mobile phase containing a gradient mixture of 0.05% v/v trifluoroacetic acid in water as mobile phase A and acetonitrile as mobile phase B at a flow rate of 0.5 ml/min. Both of the analytes were quantified with a UV detector at 245 nm. Dapivirine and DS003 were subjected to the stress conditions of oxidation, acid and base hydrolysis and thermolysis. The analytes were found to be stable under acidic and thermal conditions. Dapivirine was not significantly affected by base hydrolysis but was severely affected by oxidative conditions. DS003 was significantly affected by both oxidation and base hydrolysis. The stability-indicating capability of this method was demonstrated by adequate separation of the degradation peaks from those of the actives in the stress degraded samples. The method was validated for linearity, specificity, system suitability, precision and accuracy in accordance with ICH guidelines. The proposed method was applied to quantitate Dapivirine and DS003 in drug-excipient compatibility studies, assay of the tablets and stability studies of Dapivirine and DS003 tablets.

Background: Although initially introduced for the management of hypertension, αl-adrenergic-receptor antagonists (αlblockers) have become the standard of care for the medical management of benign prostatic hyperplasia (BPH) related lower urinary tract symptoms (LUTS). Alpha-blockers (alfuzosin, tamsulosin, doxazosin, prazosin and terazosin) relax the smooth muscles in the prostate and are indicated for the symptomatic treatment of BPH due to evidence of their positive and rapid effect on LUTS. However, these agents have the potential to produce orthostatic hypotension and other blood pressure-related adverse effects in normotensive patients and in those receiving concurrent treatment with other antihypertensive agents. As a result, more “uroselective,” less vasoactive αl-blockers have been developed such as tamsulosin and alfuzosin. Objective: The presented review provides information about the various analytical methods available in the literature to the scientists and health professionals engaged in research relating these drugs such as clinical trials or developing new formulations. Various analytical methods for the estimation of these drugs in bulk or in various matrices like blood, serum, plasma, alone or in combination with other drugs is discussed. Methods: Relevant articles were identified through a search of the English-language literature indexed in MEDLINE, PubMed, Sciencedirect and the proceedings of scientific meetings from 1977 to 2010. The search terms were benign estimation of alpha one blockers, determination of prazosin, terazosin, tamsulosin, doxazosin, alfuzosin. Similarly HPLC and Spectroscopy methods for estimation of prazosin, terazosin, tamsulosin, doxazosin, alfuzosin. Results: Total 57 analytical methods were found. 11 spectrophotometry, 39 chromatographic methods including 2 ESI MS/MS, 1 ESI MS, 2 HPTLC, 3 TLC, 17 HPLC with UV, 9 with fluorescence, 1 with electrochemical detection, 4 with MS detector. Other than this 3 voltametry, 1 method each for radioreceptor assay, polarography, capillary electrophoresis and potentiometry titrations were found. Conclusion: Radioreceptor assay, LC-MS, UPLC-MS methods were found to be the most sensitive for prazosin, terazosin and doxazosin respectively. Likewise, HPLC-MS-MS methods was found as most sensitive method for estimation of tamsulosin and alfuzosin.

It is the first systematic review to compare the bioanalytical methods to quantify the highly protein bound antimalarial, lumefantrine. We searched MEDLINE, SCIENCE DIRECT, GOOGLE and hand-searched journals and PhD theses. The inclusion criteria were, use of validated bioanalytical for quantification of lumefantrine in preclinical studies, healthy human volunteers and malaria patients. Ten bioanalytical methods were eligible and gave information on all separation and quantification domains considered in the review. There are ten previously published methods for quantitative analysis of lumefantrine in biological matrices comprising seven methods using HPLC-UV and three tandem mass spectrometric (LC-MS/MS) detection. Most of the HPLC methods incorporated complex extraction procedure and long run time. Bioanalyst(s) may choose the bioanalytical method out of reported ones depending upon the study objectives and rapidity, sensitivity and ease in sample preparation required.

Fast chiral liquid chromatographic methods are developed for the separation of bicalutamide and thalidomide enantiomers in bulk drug samples in an elution time of about 15 min. The chromatographic separation was carried out on various solvents using an amylose 3,5-dimethylphenylcarbamate immobilized onto silica gel (Chiralpak®-IA). The resolution (Rs) between the enantiomers is found to be greater than 1.5 in the developed method. Chiralpak®-IA column played a key role in achieving chromatographic resolution between the enantiomers and also in enhancing chromatographic efficiency. The column's compatability to non standard chromatographic solvents is checked and found suitable.

Counterfeiting is deeply rooted as it is being practiced since ancient times. It has been in this world for a long time, and is rapidly growing with the newly available growth in science and technology. The review provides an evidence of the growth and rising concerns of counterfeiting. Counterfeiting has been fuelled by corruption, inability to control, and also a rise in consumers who resort to such goods in the developing countries. The control of such piracy practice is indispensable and thus governments and internationally recognized institutions have taken measures to limit its spread and abolish it. The manufacturers are at a greatest loss from it and thus have started anti-counterfeiting practice. Such practice is highly recommended in healthcare practices where much harm is done to the customers. Analytical techniques and instruments have found a greater importance in the detection, identification, and differentiation of the counterfeit products. Manufacturers utilize anti-counterfeiting techniques to keep track of their product, quarantine, and identify their product from the duplicated, pirated or counterfeit products. The various anti-counterfeiting techniques are given in the review.

Drug formulations contain active pharmaceutical ingredients (APIs) and excipients. APIs present in the formulations contain some undesired impurity, which affects purity of the APIs. Therefore, with along % purity, impurity profiling is also needed to be carried out of all the APIs. Impurity profiling describes the account or description of maximum possible types of identified or unidentified impurities present in any APIs. These impurities can be API related impurities, process related impurities or stability related impurities. API related impurities include stereochemistry, crystallization, and functional group of APIs. Process related impurities include chemicals, reagents, catalysts, residual solvents, synthetic intermediate products, by product, degradation products, method conditions related impurities, and formulation related impurities. Stability related impurities include degradation or transformation of APIs, mutual interactions among APIs, excipients present in drug product. Presence of these unwanted impurities may influence bioavailability, safety and efficacy of APIs. Various regulatory authorities such as ICH, USFDA etc., have specified various limits for impurities in APIs. Along with the routine use of authentic markers and analytical techniques, isolation and characterization of impurities are required for acquiring the data that establishes biological safety and efficacy. In the recent trends impurity profiling emerges out as a mandatory requirement for a new drug application. The present review describes probable sources of impurities, need for impurity profiling and detailed techniques of characterization and quantitation of impurities. Thus, this review is an attempt to understand concept of impurity profiling and its various aspects.