Various Analytical Methodologies for Determination of Selective α<SUB>1A</SUB> Receptor Blocker Tamsulosin Hydrochloride and Its Combinations in Different Matrices

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Tamsulosin hydrochloride is the international non-proprietary name of (-)-(R)-5-[2-[[2-(o-ethoxyphenoxy) ethyl]amino]propyl]-2-methoxybenzenesulfonamide hydrochloride (Figure 1), was first developed by Yamanouchi Pharmaceuticals and is currently marketed as a single enantiomer ^[10]. Tamsulosin is a chiral molecule and its (R) enantiomer is used as a therapeutic active substance ^[11].

It has a better side effect profile than earlier α-adrenergic-receptor antagonists, which were initially developed as antihypertensive agents. Clinical trials of 1 year or longer with tamsulosin showed high tolerability for the 0.4mg dose and no significant interaction with other antihypertensive medications. Tamsulosin is a more selective α_1A subtype antagonist, which maintains the α-antagonist effect on the prostatic capsule and bladder neck but has less of an effect on the vascular system and blood pressure. In fact, tamsulosin is ineffective and not indicated in the treatment of hypertension. Tamsulosin has a favorable side effect profile in regard to problems related to hypotension and dizziness compared to those of terazosin and doxazosin ^[12].

Combining α₁-ARAs and antimuscarinic agents [e.g Tolterodine Tartarate] in the treatment of BPH resulted in statistically significant benefits in QoL scores, patient satisfaction, urinary frequency, storage symptoms and IPSS scores. The combination of α1-ARAs with antimuscarinic agents is useful for relieving symptoms of bladder outlet obstruction (BOO) and detrusor overactivity (DO). Also the combination of α1-ARAs and 5 α- reductase inhibitors [e.g. Dutesteride and Finasteride] appears to prevent disease progression in patients ^[13].

Tamsulosin is absorbed from the gastro–intestinal tract; 90% following oral administration. The extent and rate of absorption is reduced in the presence of food. It is distributed into extracellular fluid in the body. The drug is metabolised slowly in the liver by hepatic metabolism while first-pass metabolism is negligible. It is mainly metabolised by the cytochrome P₄₅₀ CYP3A enzyme and less than 10% of the dose is excreted in urine unchanged. The metabolites of tamsulosin hydrochloride undergo extensive conjugation to glucuronide or sulfate prior to renal excretion. It is excreted mainly in urine as metabolites and some unchanged drug. The apparent half–life is approximately 9 to 13 h in healthy individuals and 14 to 15 h in the target population ^[14].

Thus there is no doubt that tamsulosin is clinically important alpha one blocker. This forms the background of our study. There is clear need to study all of the analytical methods available in different matrices. Different analytical methods such as spectrophotometry, chromatography and electroanalytical methods will be discussed here. The presented study provides substantial information to the researchers involved in the development of new analytical methods and formulation development.

Review of analytical methods for the determination of five alpha one blockers was published by Shrivastava et al ^[15]. In this review authors also described tamsulosin determination methods available during the preparation of manuscript. In this paper authors focused in the determination methods of tamsulosin because of its proved clinical advantages over other alpha one blockers. This review differs in advancement of technology by inclusion of 30 more references of analytical methods for Tamsulosin.

In search for analytical methods for the determination of tamsulosin hydrochloride database like Sciencedirect, Pubmed, Medknow, NCBI, Taylor and Francis and Google scholar were explored by using keywords “Analytical methods for tamsulosin”, “Determination of tamsulosin”, “Spectrophotometric method for tamsulosin determination, “Chromatographic method for tamsulosin determination”, “Electroanalytical methods for determination of tamsulosin”. Total 82 different analytical methods were found including 24 spectrophotometry, 46 chromatography, 11 electroanalytical (including pharmacopoeia references) and 1 redioreceptor methods for the determination of tamsulosin hydrochloride either alone or in combination in different matrices.

2. Analytical Methods

Tamsulosin hydrochloride 5-[(2R)-2[[2-(2-Ethoxyphenoxy) ethyl]amino]propyl]-2-methoxybenzenesulfonamide hydrochloride is white or almost white powder slightly soluble in water, freely soluble in formic acid, slightly soluble in anhydrous ethanol. ^[16] Drug is official in JP ^[17], Eu Ph ^[16], USP ^[18] and BP ^[19].

Analytical methods for the determination of TAM are divided into three main categories, spectrophotometry, chromatography and other electroanalytical methods. Summary of all of the spectrophotometric methods are given under Table 1 and Table 2. Chromatographic methods are summarized under Table 3 and Table 4 whereas in Table 5 all electroanalytical methods for TAM determination are presented.

2.1. Spectrophotometric Methods

During the 1980s, the introduction of miniature diode array detectors, combined with powerful microprocessors and state-of-the-art mathematical tools, led to a renaissance of ultraviolet visible (UV/vis) spectrometry that enabled the rapid spread of compact, relatively low-cost, yet still powerful, laboratory UV/vis machines ^[20]. One of the interesting aspects of UV spectrophotometry is its low cost and its ease of use, allowing many measurements in a short time ^[21]. Derivative spectrophotometry, which consists in the differentiation of a normal spectrum, offers a useful means for improving the resolution of mixtures, because it enhances the detectability of minor spectral features ^[22].

Total 25 different spectrophotometric methods for the determination of TAM in either bulk or formulations are available. There is no doubt on the fact that the spectroscopic methods are rapid and far more economical than chromatographic methods, but their destructive nature and lack of sensitivity is a huge disadvantage ^{[23, 24]}. Morever, TAM has high potency (0.4mg/tab/cap) and may be this is one of the reason that spectrophotometric method or determination in biological matrices is not available. Analytical methods for the determination of tamsulosin alone is presented in Table 1 whereas Table 2 presents literatures related to combinations with other drugs.

Table 1. Summary of spectrophotometric methods for determination of Tamsulosin

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Table 2. Summary of spectrophotometric methods of Tamsulosin HCl in combination with other drugs

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Table 3. Summary of chromatographic procedures found in literature survey for the determination of Tamsulosin HCl in different matrices

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Table 4. Summary of chromatographic methods for the determination of tamsulosin HCl in combination with other drugs

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2.1.1. Comparison of Spectrophotometric Methods

Tamsulosin HCl is a potent drug [0.4/mg/cap/tab] and this is the reason there are attempts to enhance UV absorbance by addition of chromophore by some of the authors. ^{[28, 29, 30, 31, 32]}. Although UV spectrophotometric methods have advantage of simplicity and economy over chromatographic methods but it’s difficult to develop highly sensitive determinations in biological fluids. In this case there sensitivity is questionable. This may be the reason that no author till date attempted spectrophotometry method for complex matrices like biological fluids. High potency of the drug further enhances the difficulty to develop such kind of methods. However method using water for preparing dilution ^[26] seems to be most economical and simple method. Derivative spectrophotometry may be better option for resolving mixtures in simultaneous determinations. With LOD and LOQ of 0.003μg/ml 0.01μg/ml method developed by Shrivastava et al. ^[28]. is the most sensitive method available in the literature.

2.2. Chromatographic Methods

Analytical chemists have to analyze a variety of complex samples often originating in different matrices to answer questions about the quality and quantity of different analytes. These requirements are satisfied with HPLC especially if combined with an advanced detection technique such as diode array detection (DAD) or mass spectroscopy ^[40].

HPTLC allows fast and inexpensive method of analysis in the laboratory and in the field. The modern HPTLC technique, combined with automated sample application and densitometric scanning, is sensitive and completely reliable, suitable for use in qualitative and quantitative analysis. HPTLC is a valuable tool for reliable identification because it can provide chromatographic fingerprints that can be visualized and stored as electronic images ^{[41, 42]}. HPTLC remains one step ahead when compared with other tools of chromatography ^[43].

Summary of all of the chromatographic methods found in the literature survey for Tamsulosin alone and in combinations are presented under Table 3 and Table 4 respectively.

Table 5. Summary of electroanalytical methods found in literature survey

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