Article

Simultaneous determination of Telmisartan impurities and Chlorthalidone impurities by UPLC

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Abstract

A rapid specific UPLC method has been developed for simultaneous determination of Telmisartan (TS) impurities and Chlorthalidone (CT) impurities in their formulations. Chromatographic separation of these two compounds impurities was carried out an Acquity BEH Shield-RP18, 100 x 2.1 mm, 1.7 μm column is used for development of method pH 4.5 buffer is prepared using 0.025M Potassium dihydrogen phosphate, 0.0027M 1-hexane sulphonic acid sodium salt and 1 mL of triethyl amine in milli-Q water, pH 4.5 ± 0.05 adjusted with diluted ortho phosphoric acid. The mobile phase A consists pH 4.5 buffer & acetonitrile in the ratio 90:10 (v/v). Mobile phase B consists pH 4.5 buffers & acetonitrile in the ratio 20:80 (v/v). The flow rate of mobile phase is 0.3 mL/min with a gradient elution. The column temperature is 25°C and detection wavelength is 290 nm. The injection volume is 3 μL. The gradient program is as follows: time (min)/% mobile phase B: 0/20, 2/30, 5/45, 8/55, 10/80, 14/80, 14.1/20 and 18/20. The developed RPUPLC method was validated with respect to specificity, linearity, accuracy, precision, robustness and high sensitivity with detection limits and quantification limits. To the best of our knowledge, a rapid LC method, which separates all the impurities of Telmisartan and Chlorthalidone, disclosed in this investigation was not published elsewhere.

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... Different analytical methods for the determination of chlorthalidone impurities have been reported. e reported methods describe degradation studies and the estimation of assay and impurity profiles for both drug substance and drug product, as well as in combination with other drug substances [18][19][20][21][22][23]. e proposed analytical method can be performed effectively on chlorthalidone API and chlorthalidone tablets for known EPspecified, process-related, and degradation impurities. ...
... A study performed by Marineni and Sreenivasulu Reddy showed the separation of chlorthalidone, telmisartan, and its impurities, though only two chlorthalidone impurities (impurity A and impurity B) were separated with good resolution. e article does not mention the compound's specificity for degradation impurities [20]. A stability-indicating method was developed by Sonawane et al. for bulk drug and tablets using an experimental design [21]. ...
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Low-dose thiazide and thiazide-like diuretics are widely used as first-line therapy for hypertension. Chlorthalidone, a monosulfamyl diuretic, is frequently prescribed in cases of hypertension and congestive heart failure. In this research paper, an improved reverse-phase HPLC method was developed for the simultaneous identification and quantitation of pharmacopoeia-listed and in-house process- and degradation-related impurities of chlorthalidone in bulk drug and formulations. Chromatographic separation was carried out on a C8 column (250 × 4.6 mm; ‘5 μm particle size) at a flow rate of 1.4 mL/min with a 220 nm detection wavelength. Mobile phase A consisted of buffer solution (diammonium hydrogen orthophosphate (10 mM, pH 5.5)) and methanol at a 65 : 35 ratio (v/v), and mobile phase B consisted of buffer solution and methanol at a 50 : 50 ratio (v/v). The API and formulation were subjected to stress conditions such as acid, alkali, oxidation, thermal, and photolytic conditions. Validation studies for the in-house process impurities were performed for specificity, limit of detection (LOD), limit of quantitation (LOQ), linearity, precision, accuracy, and robustness. Thus, an improved RP-HPLC method capable of good separation of all known and unknown impurities with acceptable resolution and tailing factor was developed.
... A further improvement of the PD-L1 interaction was observed with two other molecules: a dimeric compound and a glucuronide derivative of TLT (Fig. 1). The TLT dimeric compound corresponds to a minor impurity detected in TLT tablets [68]. This compound has no biological relevance, but the observation suggests that an extension of the drug structure could reinforce drug binding to PD-L1. ...
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... Literature review for the TEL/CLO combination revealed several HPLC methods [9], HPTLC method [10], UPLC method [11], a UV spectrophotometric method [12] and a Spectrofluorimetric method [4]. Also, literature review of the AML/TEL/HCTZ tertiary combination revealed a UV spectrophotometric based method [13,14], chemometric assisted UV spectrophotometric methods [15], HPLC method [15], UPLC method [16], and several electrochemical methods [17][18][19][20]. ...
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