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Hindawi Journal of Analytical Methods in Chemistry Volume 2023, Article ID 5107317, 14 pages https://doi.org/10.1155/2023/5107317 Research Article Chemometric Methods for Simultaneous Determination of Candesartan Cilexetil and Hydrochlorothiazide in Binary Combinations 1,2 Diyar Salahuddin Ali Department of Chemistry, College of Science, Salahaddin University, Kurdistan Region, Erbil, Iraq Department of Medical Laboratory Science, College of Health Sciences, Lebanese French University, Kurdistan Region, Erbil, Iraq Correspondence should be addressed to Diyar Salahuddin Ali; diyar.ali@su.edu.krd Received 16 September 2022; Revised 5 December 2022; Accepted 7 January 2023; Published 17 January 2023 Academic Editor: Ricardo Jorgensen Cassella Copyright © 2023 Diyar Salahuddin Ali. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Simple, accurate, precise, and cost-efective chemometric techniques for the measurement of candesartan cilexetil and hy- drochlorothiazide in synthetic mixtures were improved and validated. H-point standard addition, Q-absorption ratio, and correction absorbance spectrophotometric techniques were utilized for the simultaneous determination of both medicines in real pharmaceutical formulations. A new calibration approach was implemented based on chemical H-point standards. Tis approach was developed to resolve signifcantly overlapping spectra of two analytes and provide direct correction of both proportional and constant errors caused by the matrix of the sample. Te frst method of simultaneous determination of candesartan cilexetil and hydrochlorothiazide was carried out using the H-point standard addition method at wavelengths 239 and 283. For the ratio of the absorption at two selected wavelengths, one of which is the isoabsorptive point and the other being the maximum of one of the two components, the second method absorption ratio method was utilized. In distilled water, the isoabsorptive point of candesartan cilexetil and hydrochlorothiazide occurs at 258 nm. λ of hydrochlorothiazide is 273 nm, which is the second wavelength used. max Lastly, the absorbance correction method was implemented. Tis approach is based on absorbance correction equations and uses distilled water as the solvent for the examination of both medicines. In NaOH/EtOH solvent, the absorbance maxima of candesartan cilexetil and hydrochlorothiazide are 250 nm and 340 nm, respectively. For both wavelengths, candesartan cilexetil and hydrochlorothiazide exhibited linearity over a concentration range of 1–46 μg/ml and 1–44 μg/ml, respectively, for H-point standard addition. Te Q-absorption ratio approach provides linearity over the concentration ranges of 1–46 μg/ml at 273 nm for candesartan cilexetil and 1–29 μg/ml for hydrochlorothiazide, 1–46 μg/ml at 258 nm for candesartan cilexetil, and 1–44 μg/ml for hydrochlorothiazide. For hydrochlorothiazide, the linearity for the correction absorbance method was obtained throughout a concentration range of 1–46 μg/ml at wavelengths 250 and 340 nm and 1–44 μg/ml at wavelength 250 nm. Te results of the analysis have been statistically and empirically supported by recovery studies. All methods yielded recoveries in the range of 96 ̶102% for both medications. Te LOD ranged from 0.46 ̶0.94 μg/mL for hydrochlorothiazide and from 1.26 ̶2.40 μg/mL for candesartan cilexetil. Te approaches were then used to quantify candesartan cilexetil and hydrochlorothiazide in pharmaceutical tablets. used mainly for the treatment of high blood pressure and 1. Introduction congestive heart failure. Candesartan has a very low Candesartan cilexetil (CAN) 2-ethoxy-1-((4-[2-(2H-1,2,3,4- maintenance dose. Hydrochlorothiazide (HCT), 6-chloro- tetrazol-5-yl) phenyl] phenyl, methyl))-1H-1, 3-benzodia- 3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1- zole-7-carboxylic acid is an angiotensin receptor blocker dioxide, is one of the oldest thiazide diuretics. Recently, 2 Journal of Analytical Methods in Chemistry CAN has been difcult to be separated from HCT in most [10]. Two straight lines with a common point in H (−C , A ) H H tablets [1, 2]. Candesartan is an efective, irreversible an- are depicted in Figure 2 [13]. tagonist because it has the highest known receptor afnity of Te measured quantity of X is added. Finally, absorbance all the ARBs, and high doses of angiotensin II (Ang II) don’t at two specifed wavelengths is measured according to the push it of the receptor. Study after study has shown the following equations: positive efects of candesartan cilexetil in the treatment of A � b + b + M C , (1) high blood pressure and heart failure (HF) [3]. For more (λ1) 0 λ1 i than 50 years, thiazide-type diuretic hydrochlorothiazide (HCT) has been available for clinical usage [4]. HCT is also (2) A � A + A + M C , (λ2) 0 λ2 i used to lower blood pressure while walking, which is mostly where A and A represent the absorbances at λ and λ caused by a drop in blood pressure at night [5]. In clinical (λ1) (λ2) 1 2, respectively, b and A represent the analytical signals of X at trials lasting anywhere from 8 weeks to 3 years, the fxed- 0 0 A and A (b ≠ A ), and b and A represent the analytical dose combination medication candesartan and hydrochlo- λ1 λ2 0 0 signals of Y at A and A (b � A ). M and M are the rothiazide has emerged as a key option in the treatment of λ1 λ2 λ1 λ2 slopes of the calibration lines at λ and λ . Lastly, C signifes hypertension due to its great efcacy in lowering blood 1 2 i the addition of X. As illustrated in Figure 2, the H-point is pressure and preventing damage to target organs [6]. dependent on the analyte concentration. Various mathematical techniques have been developed Since C � C is derived from equations (1) and (2), for the use of chemometric strategies, such as partial least i H where A � A squares, so it is possible to study drug̶excipient interactions λ1 λ2 in a single sample without resorting to costly and time- (3) b + b + M −C � A + A + M −C . 0 λ1 H 0 λ2 H consuming chemical separation [7], and multiple linear regression [8, 9], Te H-point standard addition method Hence, (HPSAM) is also used to assess binary mixtures in che- mometric techniques [10]. It was afterward changed to A − b + A − b 0 0 (4) −C � . multicomponent analysis [11–13]. Te Q-absorption ratio H M − M λ1 λ2 method [14, 15], and the correction absorbance method have also been used for binary mixture analysis [16, 17]. As interference Y has identical absorbance values at λ Several analytical methods have been reported for the and λ A � b and 2, estimation of these ingredients individually or simulta- A − b 0 0 neously, individual measurements of CAN and HCT by −C � . (5) M − M diferent analytical methods appeared in a few reported λ1 λ2 works, for an instant, valsartan look alike candesartan cilexetil Which fts within the given equation. as by high-performance liquid chromatography [18–20], gas b A chromatography–mass spectroscopy, and liquid chromatog- 0 0 −C � − � − . (6) raphy [21, 22]. Also, hydrochlorothiazide is determined by M M λ1 λ2 liquid chromatography [23, 24], capillary zone electrophoresis Tat −C is proportional to the amount of analyte [25], and spectrophotometry [26, 27]. Te combined dosage present in the mixture can be concluded [36]. of CAN and HCT was resolved simultaneously by diferent A , the intersection point’s ordinate value can be analytical methods like high-performance liquid chroma- expressed as follows: tography [28, 29], high-performance thin layer chromatog- raphy [30], liquid chromatography, mass spectroscopy A � b + b + M −C . (7) H 0 λ1 H [31, 32], liquid chromatography [33, 34], derivative spec- trophotometry [5], and the derivative ratio method [35]. As b � M from equation (7), then A � b and A � A . 0 λ1 H H In this work, HPSAM, the Q-absorbance ratio technique, Te relationship between absorbance at specifc wave- and the correction absorbance method were used for the lengths and the H-point (A ) is solely due to interference. simultaneous assessment of CAN and HCT. Tese processes Since this is the same as the zero point on the calibration were accurate, selective, sensitive, and reasonably priced. graph for the analyte when the sample is present, the an- Tese new techniques eliminate strongly overlapped spectra. alytical signal can be used to fgure out how much Y there is Te outcomes were contrasted with those attained using the from the calibration graph. HPLC technique. A simple graphical description of the Te following guidelines were used to choose the best suggested method is depicted in Figure 1. wavelength combination for the determination of CAN and HCT in a binary mixture by HPSAM: 2. Theoretical Background (1) At certain wavelengths, analyte signals must be linear to concentration, and the interferent signal must be 2.1. H-Point Standard Addition Method. Tis technique plots unafected by analyte concentration the analytical signal versus the amount of analyte at two wavelengths. Considering a sample interference, Y as the (2) Te analytical signal from a mixture combining interference and X as the analyte. For HPSAM to determine analyte and interferent should equal the sum of their X concentration, interference absorbance must be constant individual signals Journal of Analytical Methods in Chemistry 3 Drugs: Candesartan cilexetil Overlapping hydrochlorothiazide 1.35 1.2 1.05 Solution 0.9 Chemometric Techniques Scanning Problems 0.75 0.6 0.45 0.3 0.15 Wavelength nm Drug 1 Drug 2 Mixture 0.9 0.8 0.7 0.6 0.5 0.4 0.3 H.Point 0.2 (C , A ) 0.1 A H H -10 C -5 0 5 10 15 H-point Q-Absorption Ratio Correction Absorbance Standard Addition 1.6 y = 0.0304x + 0.0714 y = 0.0295x + 0.0648 R² = 0.9944 R² = 0.9926 1.4 y = 0.0272x + 0.0542 y = 0.0115x + 0.0134 1.2 R² = 0.9931 R² = 0.9968 y = 0.0145x + 0.0187 0.8 R² = 0.9944 0.6 0.4 0.2 0 10 20 30 40 50 Concentration µg (mL) Abs 283 258 Abs 239 250 Figure 1: Schematic diagram of the proposed methods. 0.9 0.8 0.7 0.6 0.5 0.4 0.3 H.Point 0.2 (C , A ) 0.1 H H -8 -6 -4 H -2 0 2 4 6 8 10 12 CONCENTRATION Figure 2: H-point standard addition method. (3) For reasonable sensitivity and accuracy, the slope 2.2. Q-Absorption Ratio Method. Tis approach is applicable diference between two straight lines measured at λ to medications that follow Beer’s law at all wavelengths and and λ must be as large as feasible [37, 38] have a consistent ratio of absorbance between any two ABSORBANCE Absorbance Absorbance ABSORBANCE 4 Journal of Analytical Methods in Chemistry wavelengths [39]. Tis method utilizes the ratio of ab- second one is the wavelength in which the analyte has no sorption at two chosen wavelengths. One represents the absorbance, the signal is only related to interference; thus, drug’s maximal absorbance, while the other represents the the absorbance of the interference at the frst wavelength was iso-absorptive point. Assume that X and Y are the two calculated as follows [42]: medications. A � A − r × A . (17) corr λ1 mix λ1 1 mix λ2 Te following equations were combined depending on this relationship: ax � ay at λ and L � 1. A , and A , are the absorbance of the mixture at 1 1 1 mixλ1 mixλ2 λ , and λ . A are the net absorbances at λ nm, Te slope 1 2 corrλ1 1 At λ A � ax C + ax C because ax � ay , (8) 1 1 1 X 1 y 1 1 ratios of the interference calibration graph are represented by the values r and r , respectively [16, 43]. 1 2 At Slope ƛ1 λ A � ax C + ay C . (9) 2 2 2 X 2 y r � . (18) Slope Equation (9) divided by equation (8), we get ax C + ay C 2 X 2 y 3. Material and Methods � . (10) A ax C + ax C 1 1 X 1 y 3.1. Apparatus. Te UV-visible spectrophotometer (UV- When F � C /C + C , F � C /C + C VIS/VIS spectrophotometer AE-S60) was connected to an x X X y y y X y identical 1.0 cm quartz cell for the UV-VIS scanning A ax F + ay − ay F 2 2 X 2 2 x � . (11) spectrum. A ax 1 1 All of the measurements in this study were estimated with the MetaSpec Pro software suite. A /A � ax F /ax − ay F /ay + ay /ay because(a 2 1 2 X 1 2 y 1 2 1 x � ay ) 1 1 Let Q � ax /ax , Q � ay /ay , Q � A /A X 2 1 Y 2 1 M 2 1 3.2. Preparation of Real Sample. Te average mass of 10 pills So Q � F Q − F Q + Q M X X y Y Y was measured, they were mashed, the powder was added to a 1 :1 NaOH : ethanol solution, and it was continuously Q − Q M Y F � . (12) stirred for 10 minutes. Te next step is the fltering pro- Q − Q X Y cedure. Tree times, 10 ml of 1 :1 NaOH : ethanol was used Equation (12), which is approximate rather than exact, to wash the powder of the flter paper. After that, the so- yields the percentage rather than the concentration of X and lution was fnished to a fnal volume of 1 L of 1 :1 NaOH : Y in the mixture. ethanol. Te solution was stored in a 4 C refrigerator. If we rearrange equation (8) to include the absolute concentrations of X and Y, we obtain the following equation: 3.3. Preparation of Standard Solution. Preparing a 1000 μg/ mL HCT solution by dissolving 0.025 gm HCT in 1 :1 C + C � . (13) x y ax NaOH : ethanol, to attain the needed analyte concentration, was diluted in a 25 mL volumetric fask. A 1000 μg/mL CAN From equations (12) and (13), we get solution was made by dissolving 0.025 gm CAN in 1 :1 C Q − Q x M Y NaOH : ethanol and was diluted in a 25 mL volumetric fask. � , (14) A /ax Q − Q Tese solutions were stored at 4 C in darkness. By serially 1 1 X Y diluting solutions with 1 :1 NaOH : ethanol, more diluted Q − Q A solutions were prepared. Tese solutions were stored at 4 C M Y 1 C � ∗ , (15) in darkness. By serially diluting solutions with 1 :1 NaOH : Q − Q ax X Y 1 ethanol, more diluted solutions were prepared. Q − Q A M Y 2 C � ∗ , (16) Q − Q ay X Y 1 3.4. 1 :1 NaOH : Ethanol Preparation. 0.2 N NaOH was prepared by dissolving 4 gm of NaOH in deionized water where C and C are the X and Y concentrations, re- x y and was diluted in a 500 mL volumetric fask. Ten mixed spectively, A , A are the absorbances of the mixture at λ , λ 1 2 1 2 with ethanol one by one to make the solvent mixture 1 :1 , ax , and ay are absorptivities of X and Y at 261 nm, and 1 1 NaOH : ethanol. ax and ay are absorptivities of X and Y at 270 nm. 2 2 Equations (15) and (16) give the absolute concentration 4. Procedures values of drug X and Y [15, 40, 41]. 4.1. H-Point Standard Addition Method. Following is the 2.3. Correction Absorbance Method. In this method, λ of general approach for determining CAN and HCT in a binary max analyte and interference was determined by scanning the combination. An aliquot of a solution containing 15 μg/mL drug solution in the UV Spectrophotometer. Which requires CAN, and 15 μg/mL HCT was added to a 2 mL volumetric two wavelengths, one is the λ of the analyte and the fask, which was then flled to the mark with deionized water. max Journal of Analytical Methods in Chemistry 5 Te solution was then allowed to stand for fve minutes at correction absorbance method when the selected pair of room temperature. Te absorbance of the solution at the wavelengths returned to the principle of the method as specifed wavelengths was then measured by transferring explained above. Te frst wavelength is 250 nm λ of max a portion of the solution into a quartz cell. Standard ad- CAN, and the second one is 340 nm for direct determination ditions of CAN ranging from 3 to 13 μg/mL were done on of HCTand applying the correction absorbance equation for the synthetic sample, which included a variable ratio of CAN the removal of the absorbance of HCT at 250 nm. Finally, to HCT. Simultaneous determination of CAN and HCT was CAN was determined at the calibration curve of standard conducted using HPSAM at two selected wavelengths. Te CAN with y � 0.0295x + 0.0648 regression equation and wavelengths selected depend on the principle of HPSAM as 0.9926 correlation coefcient, and HCT was determined at mentioned above, as well as the absorbance for the analyte the calibration curve of standard HCT with was diferent and constant for interference at selected y � 0.0054x + 0.0067 regression equation and 0.9979 corre- wavelengths of 239 and 283 nm, as shown in Figure 3, where lation coefcient. C is the unknown analyte concentration of CAN, and A is H H the analytical signal of interference HCT, was determined at 5. Linear Range 283 nm in the calibration curve of standard HCT with y � 0.0247x + 0.0297 regression equation and 0.9985 corre- Te calibration curve was drawn for selected wavelengths lation coefcient. related to the procedures of the techniques, namely, 239 and 283 nm for the HPSAM, 273 and 258 nm for the Q- absorption ratio method, and 250 and 340 nm for the 4.2. Q-Absorption Ratio Method. Te CAN and HCT in correction absorbance method. As shown in Figures 4 and 5. a binary mixture were determined by the following pro- Table 1 shows the linear range of drugs for all methods at all cedure. Te mixtures of standard solutions of the drugs were wavelengths. prepared with a 2 mL volumetric fask, in diferent con- centration ratios in the range of 11–19 μg/mL by diluting the 6. Limit of Detection (LOD) and Limit of appropriate volume of a stock solution of each drug with deionized water, then the solution was transferred to Quantification (LOQ) a quartz cell to scan in the range of 200–400 nm. Te de- 6.1. H-Point Standard Addition Method and Correction Ab- termination is carried out by Q-absorption ratios at two sorbance Method. Equations (20) and (21) provide the selected wavelengths. Te selection of wavelengths was computations for the limit of detection (LOD) and limit of carried out related to the principle of the Q-Absorption ratio quantifcation (LOQ) for the H-point standard addition method, where one of these wavelengths is the iso-absorptive method and correction absorbance method. point and the other one is the max of one of the drugs. After diferent wavelengths were tested, 273 nm was selected as LOD � X + 3SD , (20) b b λ of HCT and 258 nm as the iso-absorptive point of CAN max and HCT for applying the Q-absorption ratio procedure, as LOQ � X + 10SD , (21) b b shown in Figure 3. HCT and CAN were determined at 273 and 258 nm with a Q-absorption ratio in the following where X represents the concentration of fve replications equations: (n � 5) and SD is the standard deviation of the blank [13]. Te corresponding values obtained for HCT were 0.46 μg/ Q − Q A M Y 1 C � ∗ , mL LOD and 0.91 μg/mL LOQ, and for CAN, they were Q − Q ax X Y 1 0.48 μg/mL LOD and 1.26 μg/mL LOQ in HPSAM as shown (19) in Tables 2 and 3, and 0.93 μg/mL LOD and 2.1 μg/mL LOQ Q − Q A M Y 2 C � ∗ , for HCT and 0.94 μg/mL LOD and 2.4 μg/mL LOQ for CAN Q − Q ay X Y 1 in the correction absorbance method as shown in Tables 4 where C and C are the HCT, and CAN concentrations, and 5. x y respectively, A andA are the absorbances of the mixture at 1 2 λ and λ , ax , and ay are absorptivities of HCTand CAN at 1 2 1 1 6.2. Q-Absorption Ratio Method. Calibration curves were 273 nm, and ax and ay are absorptivities of HCTand CAN 2 2 used to fgure out the LOD and LOQ of the new method by at 258 nm. the following equation: 3.3 σ 4.3. Correction Absorbance Method. Te following pro- LOD � , cedure was applied for the determination of HCT and CAN (22) with the correction absorbance method. Te series standard 10 σ LOQ � , solution was prepared by transferring the aliquot amounts of stock solution to a 2 mL volumetric fask and completed to the mark with deionized water. Te solution was then where σ is the standard deviation of the blank and S is the poured into the 1 cm quartz cell and scanned in the range of slope of the calibration curve. Table 6 shows the LOD and 200–400 nm. HCT, and CAN were determined by the LOQ for those drugs [14]. 6 Journal of Analytical Methods in Chemistry 1.35 1.2 1.05 0.9 0.75 0.6 0.45 0.3 0.15 230 240 250 260 270 280 290 300 310 320 330 340 350 360 Wavelength nm CAN 15 µg/ml HCT 15 µg/ml Mixture Figure 3: Absorption spectra of 15 μg/ml candesartan cilexetil and 15 μg/ml hydrochlorothiazide. 1.6 y = 0.0295x + 0.0648 y = 0.0304x + 0.0714 R² = 0.9926 R² = 0.9944 1.4 y = 0.0115x + 0.0134 y = 0.0272x + 0.0542 R² = 0.9968 R² = 0.9931 1.2 y = 0.0145x + 0.0187 R² = 0.9944 0.8 0.6 0.4 0.2 0 5 101520253035404550 Concentration µg (mL) Abs 283 258 Abs 239 250 Figure 4: Calibration graph of candesartan cilexetil at 283, 273, 258, 250, and 239 nm. correction absorbance technique, respectively, accuracy 7. Accuracy and Precision was expressed as a percentage error, which was displayed By using the methods for assessing various ratios of the in Tables 7–9. drug combination, the suggested methods’ accuracy was Additionally, the accuracy of the suggested procedures evaluated, by preparing the following combinations for was examined by measuring the drug concentrations in CAN and HCT, respectively (15 : 11, 15 : 13, 15 : 15, 17 : 15, a 15 g/mL combination fve times in a row. For the H-point and 19 : 15) μg/mL. Ten, using the relevant regression standard addition method, Q-absorption ratio method, and equation, all the suggested techniques were used to obtain correction absorbance technique, respectively, the accuracy the desired concentration. For the H-point standard ad- of each approach is shown as a percentage of the relative dition method, Q-absorption ratio method, and standard deviation in Tables 10–12. Absorbance Absorbance Journal of Analytical Methods in Chemistry 7 2.5 y = 0.0444x + 0.0436 y = 0.0274x + 0.0297 y = 0.0249x + 0.0364 R² = 0.9971 R² = 0.9991 R² = 0.9991 y = 0.0247x + 0.0297 y = 0.0054x + 0.0067 R² = 0.9979 R² = 0.9985 1.5 y = 0.0236x + 0.0311 R² = 0.9992 0.5 0 5 101520253035404550 Concentration µg (mL) Abs 283 abs 250 Abs 239 abs 273 abs 340 abs 258 Figure 5: Calibration graph of hydrochlorothiazide at 340, 283, 273, 258, 250, and 239 nm. Table 1: Linearity of drugs at all proposed methods. Candesartan Hydrochlorothiazide Method Wavelength (nm) cilexetillinearity (μg/mL) linearity (μg/mL) 239 1–46 1–44 HPSAM 283 1–46 1–44 273 1–46 1–29 Q-absorption ratio method 258 1–46 1–44 250 1–46 1–44 Correction absorbance method 340 1–46 Table 2: Limit of detection (LOD) and limit of quantifcation (LOQ) of HCT by HPSAM. Added (μg/mL) Found (μg/mL) Λ Regression equation R HCT CAN HCT CAN 283 Y � 0.01158 X + 0.1783 0.9915 15 15 0.21 14.9 239 Y � 0.03315 X + 0.4996 0.9955 283 Y � 0.01152 X + 0.1767 0.9905 15 15 0.2 14.85 239 Y � 0.03315 X + 0.4978 0.9955 283 Y � 0.01147 X + 0.1813 0.9911 15 15 0.33 15.02 239 Y � 0.03295 X + 0.5039 0.9962 283 Y � 0.01141 X + 0.1787 0.9917 15 15 0.23 15.12 239 Y � 0.03276 X + 0.5014 0.9968 283 Y � 0.01136 X + 0.1800 0.9922 15 15 0.33 15.05 239 Y � 0.03282 X + 0.5029 0.9967 Mean 0.26 SD 0.065 LOD 0.46 LOQ 0.91 ∗1 calculated using the regression equation of Y � 0.0247X + 0.0297 and the HCT calibration curve at 283 nm. Absorbance 8 Journal of Analytical Methods in Chemistry Table 3: Limit of detection (LOD) and limit of quantifcation Table 5: Limit of detection (LOD) and limit of quantifcation (LOQ) of CAN by HPSAM. (LOQ) of CAN by correction absorbance. Added Found Added (μg/mL) Found (μg/mL) (μg/mL) (μg/mL) λ Regression equation R HCT CAN HCT CAN HCT CAN HCT CAN 15 0 14.61 0.54 283 Y � 0.01152 X + 0.4192 0.9905 250 15 15 15.2 0.07 239 Y � 0.03433 X + 0.4208 0.9962 15 0 1482 0.45 283 Y � 0.01103 X + 0.4202 0.9944 250 15 15 15.13 0.33 239 Y � 0.03432 X + 0.4278 0.9925 15 0 14.96 0.036 283 Y � 0.01245 X + 0.4128 0.9904 250 15 15 15.02 0.05 239 Y � 0.03637 X + 0.4116 0.9945 15 0 14.88 0.51 283 Y � 0.01103 X + 0.4154 0.9944 250 15 15 15.03 0.14 239 Y � 0.03386 X + 0.4185 0.9922 15 0 14.93 0.39 283 Y � 0.01141 X + 0.4182 0.9917 250 15 15 15.25 0.16 239 Y � 0.03510 X + 0.4144 0.9977 Mean 0.39 Mean 0.15 SD 0.2035 SD 0.111 LOD 0.94 LOD 0.48 LOQ 2.4 ∗1 LOQ 1.26 calculated using the regression equation of Y � 0.0236x + 0.0311, and the HCT calibration curve at 283 nm. calculated using the regression equation of Y � 0.0054x + 0.0067 and the ∗2 HCT calibration curve at 340 nm. calculated using the regression equation of Y � 0.0295x + 0.0648 and the HCT calibration curve at 250 nm. insoluble in 1 :1 NaOH : ethanol, also, the result of the methods in the determination of drug in the presence of Table 4: Limit of detection (LOD) and limit of quantifcation soluble interferences shows a good percentage recovered (LOQ) of HCT by correction absorbance. shows that there is no interference from these supplement additives with the methods applied. Te results obtained in Added (μg/mL) Found (μg/mL) Tables 13–15 reveal a great degree of accuracy for all HCT CAN HCT CAN methods. 0 15 0.65 14.67 340 9. Application 0 15 0.23 14.8 Tese procedures and methods have been used in phar- 0 15 0.56 14.91 maceutical formulations (tabs) and synthetic lab mixtures to assess the analytical applicability of the intended method- 0 15 0.45 14.89 ologies. Tese methods are frequently used for simultaneous determination. All of our methods’ results were contrasted 0 15 0.38 14.8 with the HPLC result, which served as the benchmark. Te HPSAM was used for the simultaneous estimation of HCT Mean 0.45 and CAN in the synthetic mixture and pharmaceutical SD 0.1623 formulation. Te results are listed in Table 16. Te Q-analysis LOD 0.93 technique procedure was efectively used to determine the LOQ 2.1 ∗ amounts of HCT and CAN by being repeated three times calculated using the regression equation of Y � 0.0236x + 0.0311 and the HCT calibration curve at 283 nm. within the synthetic lab mixture and pharmaceutical for- mulation, as shown in. Table 17, the results of the correction absorbance technique for simultaneous determination of HCTand CAN 8. Interferences in the pharmaceutical formulation, are shown in Table 18. Te value of the real samples was calculated for each of the Te tolerance limit was described as the concentration of the tablets by the HPLC method. According to the tables, the added species interference (such as lactose monohydrate, methods presented in this work are sufciently general to be magnesium stearate, stearic acid, polyethylene glycol, starch, applied to fgure out the HCT and CAN of a real sample of sucrose, Na CO , and NaHCO ) causing an error of more 2 3 3 than ±5% on the analytical signal, and then, before the tablets simultaneously. beginning of the process with the analysis of the compound under study in pharmaceutical dosage forms, it was con- 10. Results and Discussion ducted to discover its efect. Samples were prepared by mixing known quantities of the investigated drugs with Based on the results, we made the following observations. diferent quantities of mutual excipients. Te result shows Experimental evaluation of the HPSAM, Q-absorption magnesium stearate, stearic acid, and Na CO were ratio, and correction absorption methods in this work 2 3 Journal of Analytical Methods in Chemistry 9 Table 6: LOD and LOQ for HCT and CAN by the Q-absorbance ratio method. Parameter Hydrochlorothiazide Candesartan cilexetil Determination wavelength 273 nm λ 258 nm isoabsorptive point max LOD (μg/mL) 0.76 0.88 LOQ (μg/mL) 1.93 2.1 Table 7: Accuracy of the H-point standard addition method in the determination of HCT and CAN. Hydrochlorothiazide (HCT) Candesartan cilexetil (CAN) (μg/mL) (μg/mL) λ Regression equation R Add Found %E Add Found %E 283 Y � 0.01141 X + 0.5420 0.9917 15 15.3 1.7 11 10.7 2.9 239 Y � 0.03298 X + 0.7723 0.9961 283 Y � 0.01147 X + 0.5494 0.9911 15 14.6 2.8 13 12.9 0.7 239 Y � 0.03315 X + 0.8294 0.9955 283 Y � 0.01141 X + 0.5917 0.9917 15 15.4 2.5 15 14.7 1.8 239 Y � 0.03309 X + 0.9109 0.9957 283 Y � 0.01154 X + 0.6523 0.9903 17 16.97 0.18 15 15.45 3 239 Y � 0.03327 X + 0.9882 0.9950 283 Y � 0.01155 X + 0.6745 0.9902 19 19.1 0.5 15 15.14 0.9 239 Y � 0.03312 X + 1.001 0.9956 calculated using the regression equation of Y � 0.0247x + 0.0297, and the HCT calibration curve at 283 nm. Table 8: Accuracy of the Q-absorption ratio method in the determination of HCT and CAN. Hydrochlorothiazide (μg/mL) Candesartan cilexetil (μg/mL) Add Found %E Add Found %E 15 14.8 −1.3 11 11.3 2.73 15 14.57 −2.76 13 12.48 −3.98 15 15.02 0.13 15 15.03 0.2 17 16.9 −0.59 15 14.96 −0.27 19 18.77 −1.2 15 14.85 −1 Table 9: Accuracy of the correction absorbance method in the determination of HCT and CAN. Hydrochlorothiazide (μg/mL) Candesartan cilexetil (μg/mL) Add Found %E Add Found %E 15 15.12 0.8 11 11.01 0.1 15 14.45 −3.66 13 12.7 −2.29 15 15.31 2.06 15 14.86 −0.95 17 16.54 −2.73 15 14.6 2.6 19 19.51 2.67 15 14.87 −0.9 ∗1 ∗2 calculated using the regression equation of Y � 0.0054x + 0.0067 and the HCT calibration curve at 340 nm. calculated using the regression equation of Y � 0.0295x + 0.0648 and the HCT calibration curve at 250 nm. 10 Journal of Analytical Methods in Chemistry Table 10: Precision of the H-point standard addition method in the determination of HCT and CAN. Added (μg/mL) Found (μg/mL) λ Regression equation R HCT CAN HCT CAN 283 Y � 0.01103 X + 0.5816 0.9944 15 15 15.12 14.98 239 Y � 0.03188 X + 0.8939 0.9989 283 Y � 0.01096 X + 0.5688 0.9945 15 15 14.75 14.86 239 Y � 0.03194 X + 0.8805 0.9985 283 Y � 0.01141 X + 0.5638 0.9917 15 15 14.43 14.59 239 Y � 0.03260 X + 0.8730 0.9974 283 Y � 0.01108 X + 0.5719 0.9941 15 15 14.71 15.06 239 Y � 0.03187 X + 0.8850 0.9989 283 Y � 0.01103 X + 0.5793 0.9944 15 15 15.17 14.64 239 Y � 0.03186 X + 0.8843 0.9989 Mean 14.84 14.83 SD 0.3084 0.2061 RSD 2.08 1.39 (n � 5) %R 98.9 98.84 calculated using the regression equation of Y � 0.0247x + 0.0297 and the HCT calibration curve at 283 nm. Table 11: Precision of the Q-absorption ratio method in the de- Table 12: Precision of the correction absorbance method in the termination of HCT and CAN. determination of HCT and CAN. Added (μg/mL) Found (μg/mL) Added (μg/mL) Found (μg/mL) λ λ HCT CAN HCT CAN HCT CAN HCT CAN 273 340 15 15 14.78 14.84 15 15 14.72 14.71 258 250 273 340 15 15 15 15 15 15 15.22 15.23 258 250 273 340 15 15 15 15 15 15 15.13 14.93 258 250 273 340 15 15 14.6 15.1 15 15 15.27 15.14 258 250 273 340 15 15 15 15 15 15 15.2 15.24 258 250 Mean 14.88 14.99 Mean 15.11 15.05 SD 0.1813 0.09338 SD 0.2226 0.2273 RSD 1.22 0.63 RSD 1.47 1.51 (n � 5) (n � 5) %R 99.2 99.93 %R 100.73 100.33 ∗1 calculated using the regression equation of Y � 0.0054x + 0.0067 and the HCT calibration curve at 340 nm. calculated using the regression led us to consider these methods efective for the si- equation of Y � 0.0295x + 0.0648 and the HCT calibration curve at 250 nm. multaneous determination of HCT and CAN. Our results that were presented in this work are generally sufcient to be applied to real samples in pharmaceutical formula- HPSAM, Q-absorption ratio, and absorbance correction tions. Te efectiveness of the proposed methods has been to simultaneously determine HCT and CAN. We can substantiated in Table 19. Te spectra of the binary come up with some hypotheses regarding the re- mixture that was prepared in accordance with Section 3.3 producibility of the procedure based on the outcomes of are shown in Figure 1. As can be seen, the samples’ the fve separate measurements. Te proposed methods were validated according to the ICH recommendations analytes and interference spectra exhibit signifcant wavelength range overlap. Following the testing of nu- [44]. Tese methods were utilized successfully to estimate the quantities of candesartan, cilexetil, and hydrochlo- merous wavelength pairings for the use of HPSAM, Q- absorption ratio, and correction absorbance methods, rothiazide in commercially available tablet formulations HCT and CAN function in this technique as analyte and containing candesartan cilexetil and hydrochlorothiazide. interference. Te fndings indicate that 239 and 283 nm Tree tablet formulations were used as samples in this are best for determining CAN and HCT by HPSAM, while study, one of these samples is Candex which contains in its 273 and 258 nm are best for the Q-absorption ratio, fnally, composition 12.07 mg per tablet of HCT and 15.89 mg per 250 and 340 nm were chosen for the correction absor- tablet of CAN as analyzed by the standard method using bance method, because there is no interference at these HPLC. Using the H-point standard addition method, the wavelengths. In light of this, we proposed new methods: amount of HCT was found to be 12.08 mg and the amount Journal of Analytical Methods in Chemistry 11 Table 13: Efect of interferences on the H-point standard addition method. HCT (μg/mL) CAN (μg/mL) Type of Amount of λ Regression equation R interferences interferences (μg/mL) Add Found %E Add Found %E 283 Y � 0.01202 X + 0.5936 0.9946 Polyethylene glycol 100 15 14.98 0.15 15 15.08 0.51 239 Y � 0.03424 X + 0.9286 0.9901 283 Y � 0.01219 X + 0.6102 0.9923 Sucrose 100 15 15.6 4.07 15 14.8 −1.35 239 Y � 0.03424 X + 0.9365 0.9901 283 Y � 0.01155 X + 0.6039 0.9902 Lactose 100 15 15.5 3.4 15 15.3 2 239 Y � 0.03353 X + 0.9402 0.9938 283 Y � 0.01165 X + 0.5931 0.9965 Starch 100 15 14.96 0.29 15 15.6 3.74 239 Y � 0.03449 X + 0.9485 0.9995 283 Y � 0.01115 X + 0.5776 0.9974 NaHCO 100 15 14.95 0.34 15 14.89 −0.74 239 Y � 0.03320 X + 0.9059 0.9993 283 Y � 0.01197 X + 0.6095 0.9967 All of above 100 15 15.5 3.4 15 15.23 1.54 239 Y � 0.03407 X + 0.9461 0.9996 calculated using the regression equation of Y � 0.0247x + 0.0297 and the HCT calibration curve at 283 nm. Table 14: Efect of interferences on the Q-absorption ratio method. HCT (μg/mL) CAN (μg/mL) Type of Amount of interferences interferences (μg/mL) Add Found %E Add Found %E Polyethylene glycol 100 15 15.36 2.4 15 15.41 2.7 Sucrose 100 15 14.43 −3.8 15 15.46 3.1 Lactose 100 15 15.18 1.18 15 15.15 1 Starch 100 15 14.9 −0.6 15 15.4 2.9 NaHCO 100 15 14.97 −0.2 15 15.36 2.8 All of above 100 15 15.25 1.68 15 14.8 −1.3 Table 15: Efect of interferences on the correction absorbance method. HCT (μg/mL) CAN (μg/mL) Type of Amount of interferences interferences (μg/mL) Add Found %E Add Found %E Polyethylene glycol 100 15 15.53 3.5 15 15.34 2.5 Sucrose 100 15 15.24 1.6 15 15.2 1.3 Lactose 100 15 14.4 −4 15 14.62 −2.5 Starch 100 15 15.18 1.2 15 15.13 0.92 NaHCO 100 15 14.62 −2.5 15 15.34 2.3 All of above 100 15 15.47 3.1 15 15.11 0.74 1 2 ∗ ∗ calculated using the regression equation of Y � 0.0054x + 0.0067 and the HCT calibration curve at 340 nm. calculated using the regression equation of Y � 0.0295x + 0.0648 and the HCT calibration curve at 250 nm. 12 Journal of Analytical Methods in Chemistry Table 16: Statistical comparison between the HPSAM and HPLC. HCT milligram/tablet CAN milligram/tablet No Name HPLC HPSAM %E % recovery HPLC HPSAM %E % recovery 1 Awacand 11.75 11.68 −0.6 100.6 14.98 15.05 0.48 99.52 2 Candex 12.07 12.08 0.083 99.917 15.89 15.79 −0.64 100.64 3 Atacand 11.92 11.99 0.59 99.41 15 14.83 −1.16 101.16 calculated using the regression equation of Y � 0.0247x + 0.0297 and the HCT calibration curve at 283 nm. Table 17: Statistical comparison between the Q-absorption ratio method and HPLC. HCT milligram/tablet CAN milligram/tablet NO Name HPLC Q-Abs %E % recovery HPLC Q.Abs %E % recovery 1 Awacand 11.75 11.57 −1.45 98.47 14.98 15.14 1.1 101.0 2 Candex 12.07 12.1 0.22 100.2 15.89 15.9 0.17 100.06 3 Atacand 11.92 11.88 −0.33 99.66 15 15.02 0.13 100.13 Table 18: Statistical comparison between the correction absorbance method and HPLC. HCT milligram/tablet CAN milligram/tablet NO Name HPLC Correction method %E % recovery HPLC Correction method %E % recovery 1 Awacand 11.75 11.41 2.9 97.1 14.98 15.07 −0.6 100.6 2 Candex 12.07 12.56 −3.9 104.1 15.89 16.21 −2 102 3 Atacand 11.92 12.1 −1.5 101.5 15 14.4 4 96 1 2 ∗ ∗ calculated using the regression equation of Y � 0.0054x + 0.0067 and the HCT calibration curve at 340 nm. calculated using the regression equation of Y � 0.0295x + 0.0648 and the HCT calibration curve at 250 nm. Table 19: Te review of the published work for simultaneous determination of drugs by diferent chemical methods. No Method Drug Linear range (μg/ml) RSD% Recovery% LOD (μg/ml) Reference CAN 2.5–50 1.19 99.0 0.55 1 Spectrophotometric [45] HCT 1–30 0.74 99.0 0.32 CAN 2–24 0.205 101.2 — 2 UV-spectrophotometric [46] HCT 2–24 0.154 99.2 — CAN 6.25–18.75 — 99.78 0.410 3 RP-HPLC [47] HCT 8–24 — 100.64 0.699 CAN 1–46 0.2061 98.84 0.48 4 Proposed methods (HPSAM) — HCT 1–44 0.3084 98.9 0.46 CAN 1–46 0.09338 99.93 0.88 5 Proposed methods (Q-absorption ratio) — HCT 1–44 0.1813 99.2 0.76 CAN 1–46 0.2273 100.33 6 Proposed methods (correction absorbance) — HCT 1–44 0.2226 100.73 of CAN was found to be 15.79 mg, which correspond to 11. Conclusion 99.917 percent and 100.64 percent of the w/w label claim, respectively. Using the Q-absorption ratio method, the A brand-new, straightforward, quick, and sensitive approach is suggested for the analysis of two binary mixtures with amount of HCT was found to be 12.1 mg and the amount of CAN was found to be 15.9 mg, which corresponds to overlapping spectra. Te process starts with the creation of absorbance ratio spectra, then moves on to measuring peak- 100.2 percent and 100.06, respectively. Te last method used in this study is the correction absorbance method, to-trough amplitudes. Te suggested methods have various and the amount of HCT found in the tablet formulation advantages over conventional spectrophotometric methods was 12.56 mg for HCT and 16.21 mg for CAN, which for the resolution of binary mixtures, including the lack of corresponds to 104.1 and 102 percent, respectively. For all a need for complex mathematical handling of the absorption medicines, recovery and error percentages were used to data. In an ongoing study, straightforward and efective calculate accuracy. Te data comparison between our chemometric methods like H-point standard addition, q- absorption ratio, and correction absorbance methods were methods and the standard HPLC method is shown in Tables 16–18. devised for the simultaneous measurement of Journal of Analytical Methods in Chemistry 13 [12] P. C. n. Falco, ´ J. V. Andres, ´ and F. B. Reig, “Evaluation and hydrochlorothiazide and candesartan in bulk and in the elimination of the blank bias error using the HPSAM in the pharmaceutical dosage form. It was found that the validity of simultaneous spectrophotometric determination of two these methods could be demonstrated through the accurate species,” Analytica Chimica Acta, vol. 348, pp. 39–49, 1997. and precise determination of drug combinations in a variety [13] M. W. Sabr and D. S. Ali, “H-point standard addition method of laboratory-prepared mixtures and pharmaceutical tablets. for simultaneous determination of phenylephrine hydrochlo- Consequently, the methodology proposed here is suitable for ride, chlorpheniramine maleate, and paracetamol as a ternary routine quality control of these set mixtures. mixture in pharmaceutical formulations,” Journal of the Indian Chemical Society, vol. 99, no. 7, Article ID 100526, 2022. [14] G. Pandey and B. Mishra, “A new analytical Q-absorbance Data Availability ratio method development and validation for simultaneous estimation of lamivudine and isoniazid,” International Te data used to support the fndings of this study are in- Scholarly Research Notices, vol. 2013, Article ID 912376, cluded within the article. 5 pages, 2013. [15] G. Singh, D. Kumar, D. Sharma, M. Singh, and S. 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Journal of Analytical Methods in Chemistry – Hindawi Publishing Corporation
Published: Jan 17, 2023
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