87urn:lsid:arphahub.com:pub:A116C711-4C18-5A38-8F1E-5E97753A8A64Folia MedicaFM0204-80431314-2143Plovdiv Medical University10.3897/folmed.68.e169306169306Research ArticlePharmacyDevelopment and validation of a UV-spectrophotometric method for determination of an ACE inhibitor in pharmaceutical formulationsGvozdevaYanayana.gvozdeva@mu-plovdiv.bghttps://orcid.org/0000-0002-7622-6060123Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv, BulgariaCenter for Competence “PERIMED-2”, Medical University of PlovdivPlovdivBulgariaResearch Institute, Medical University of Plovdiv, Plovdiv, BulgariaFaculty of Pharmacy, Medical University of PlovdivPlovdivBulgariaCenter for Competence “PERIMED-2”, Medical University of Plovdiv, 4002 Plovdiv, BulgariaResearch Institute, Medical University of PlovdivPlovdivBulgaria
Corresponding author: Yana Gvozdeva, Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, Medical University of Plovdiv, 15A Vassil Aprilov Blvd., 4002 Plovdiv, Bulgaria; Email: yana.gvozdeva@mu-plovdiv.bg
202624022026681e169306F528F1BC-7865-51B9-AA71-A70DF7E5A83B2008202513102025Yana GvozdevaThis is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Introduction: Fosinopril sodium, an angiotensin-converting enzyme inhibitor, is a widely prescribed antihypertensive agent and one of the leading drugs approved for use in hypertension management. Despite its clinical relevance, no UV-spectrophotometric methods have been previously reported for the analysis of fosinopril sodium in simulated salivary fluid (SSF, pH 6.8) and simulated gastric fluid (SGF, pH 1.2). However, researchers favor UV-spectrophotometry due to its versatility, simplicity, and efficiency in drug analysis.
Aim: The aim of this study was to develop and validate a simple, rapid, and cost-effective UV-spectrophotometric method for analyzing fosinopril sodium in both experimental and commercial dosage forms, as well as in novel drug delivery systems.
Materials and methods: This study presents the development of a UV-spectrophotometric method for quantifying fosinopril sodium in enzyme-free SSF and SGF media and its validation.
Results: Maximum absorbance is observed at 209 nm in SSF and 207 nm in SGF. The technique demonstrates linearity in the range of 2.5–20 μg/mL, with a limit of detection and limit of quantification of 0.0438 μg/mL and 0.133 μg/mL in SSF, and 0.0714 μg/mL and 0.216 μg/mL in SGF, respectively. Analytical recovery is 100.1% in SSF and 99.9% in SGF, with RSD values of 0.373% in SSF and 0.203% in SGF, indicating high precision and accuracy.
Conclusion: These results demonstrate that the developed and validated method is suitable for the routine quantitative determination of fosinopril sodium in experimental and commercial pharmaceutical formulations.
Gvozdeva Y. Development and validation of a UV-spectrophotometric method for determination of an ACE inhibitor in pharmaceutical formulations. Folia Med (Plovdiv) 2026;68(1):е169306. doi: 10.3897/folmed.68.e169306.
Introduction
Fosinopril sodium (FOS) (2S,4S)-4-cyclohexyl-1-(2-{[2-methyl-1-(propanoyloxy) propoxy](4-phenylbutyl)phosphoryl}acetyl)pyrrolidine-2-carboxylate (FOS), is a phosphate-containing angiotensin-converting enzyme (ACE) inhibitor.[1]Fig. 1 shows the chemical structure of FOS.
472299E0-687E-5BD2-AB93-603D458A4428
Chemical structure of fosinopril sodium.
https://binary.pensoft.net/fig/1547943
FOS is a white to off-white crystalline powder. It is soluble in water (100 mg/mL), methanol and ethanol, and slightly soluble in hexane.[2] After oral administration, FOS, which is an ester prodrug, is quickly converted into its main active metabolite, fosinoprilat, through hydrolysis.[3] The oral absorption of fosinopril varies with its dosage form, ranging from approximately 32% for solution formulations to about 36% for capsule forms. Following hydrolysis, the oral bioavailability of fosinoprilat averages around 25% for solution formulations and approximately 29% for capsule forms.[4]
Fosinopril is approved by the U.S. Food and Drug Administration (FDA) for managing hypertension and heart failure, alongside other ACE inhibitors like captopril, enalapril, lisinopril, benazepril, quinapril, ramipril, moexipril, and trandolapril. As a competitive inhibitor of angiotensin-converting enzyme (ACE), fosinopril blocks the transformation of angiotensin I into angiotensin II, a potent vasoconstrictor.[5] In addition to its approved uses, fosinopril is prescribed off-label for conditions such as acute myocardial infarction, diabetic nephropathy, and HIV-related kidney disease.[6] Compared to drugs like enalapril and captopril, fosinopril is notable for its longer half-life, greater water solubility, and stability against liver metabolism. It is an effective ACE inhibitor for hypertension treatment and can be used alone or in combination with other medications to manage high blood pressure or heart failure. FOS offers a safer antihypertensive option compared to other ACE inhibitors due to its elimination from the body through both renal and hepatic pathways.[7] Additionally, ACE inhibitors are shown to possess renoprotective properties in adults. They work by inhibiting local growth and inflammatory mediators, which in turn helps reduce glomerular hypertrophy, sclerosis, tubulointerstitial inflammation, and fibrosis. Given that childhood hypertension is most often secondary to renal parenchymal disease, ACE inhibitors are considered highly effective antihypertensive agents in pediatric patients.[8] The standard pediatric dosage of FOS for children weighing more than 50 kilograms (110 pounds) is 5 to 10 mg administered once daily.[9]
Numerous studies indicate that the renin-angiotensin system (RAS) plays a role in the progression of various malignancies. De Paepe et al.[10] observe that increased expression of the angiotensin II type 1 receptor may contribute to the development of breast hyperplasia, a known precursor to breast cancer. Additionally, researches have shown that ACE inhibitors and angiotensin receptor blockers may lower the risk of certain cancers, including esophageal carcinoma[11] and keratinocyte carcinoma[12]. While the involvement of RAS in the development of hepatocellular carcinoma remains not fully understood, Saber et al.[13] demonstrate that fosinopril, at a dose of 2 mg/kg, exhibits a potential anti-tumor effect in a diethylnitrosamine-induced hepatocellular carcinoma model, showing promising results when compared to sorafenib at 30 mg/kg.
Linlin et al.[14] demonstrate that the combination of tripterygium glycosides and fosinopril produces favorable clinical outcomes in the treatment of pediatric patients with Henoch-Schönlein purpura nephritis. This therapeutic effect is associated with improvements in clinical symptoms, potentially mediated by a reduction in IgA levels, suppression of cellular immune responses, and enhancement of coagulation function.
Furthermore, ACE inhibitors have positive effects in slowing the progression of diabetic retinopathy in patients with type II diabetes and demonstrate potential benefits in managing age-related macular degeneration.[15] ACE inhibitors are a promising class of drugs for reducing intraocular pressure (IOP), offering potential therapeutic benefits in the treatment of glaucoma. By inhibiting ACE, these drugs increase bradykinin levels and stimulate the production of prostaglandins, which may help lower IOP by enhancing uveoscleral outflow.[16] Among them, FOS – an ester prodrug of fosinoprilat and the first orally active phosphorus-containing ACE inhibitor – stands out as a promising candidate for IOP reduction.[17]
In recent years, ACE inhibitors have garnered growing scientific interest for their therapeutic potential beyond the management of hypertension. Among these, FOS, which has been approved for clinical use since 1990, including in pediatric populations, is the subject of extensive pharmacological investigation.[18] The advancement of novel drug delivery systems incorporating FOS consequently underscores the necessity for robust, precise, and validated analytical methodologies for its quantitative determination in pharmaceutical formulations such as tablets.
Ultraviolet (UV) spectroscopy has been a vital analytical tool in the pharmaceutical industry for over 35 years. It is primarily used to measure the absorption of monochromatic light by colorless compounds within the near UV region of the spectrum (200–400 nm) and can be applied to both solutions and solid samples to obtain their absorbance spectra.[19] That is why UV-visible spectrophotometry is a widely utilized analytical technique in pharmaceutical analysis, particularly suitable for the quantification of active pharmaceutical ingredients in drug delivery systems and dosage forms. The European Pharmacopoeia (Ph. Eur.) employs high-performance liquid chromatography (HPLC) coupled with UV detection to quantify FOS in pharmaceutical preparations.[20] There are only a few research articles that show the development of an HPLC method for FOS quantification.[21-27] Тherefore, the objective of this study was to develop and validate a UV-spectrophotometric method for the quantification of FOS in two different dissolution media: enzyme-free artificial saliva (phosphate buffer, pH 6.8) and enzyme-free artificial gastric fluid (buffer, pH 1.2). The method is systematically validated according to key analytical parameters, including specificity, linearity, working range, stability, detection limit, determination limit, repeatability, reproducibility, and analytical yield. The development of a method for quantitative determination of a drug in simulated gastric fluid without enzymes and simulated salivary fluid without enzymes is necessary for the characterization of orodispersible tablets. Orally disintegrating tablets with FOS will be prepared for the purpose of pediatric antihypertensive therapy, which is our next step.
Aim
The aim of the study was to develop and validate a simple, less time-consuming, and cost-effective analytical UV-spectrophotometric method for determining fosinopril sodium in experimental and commercial dosage forms and innovative drug delivery systems. The analytical procedure is performed in enzyme-free simulated saliva (pH=6.8) and enzyme-free simulated gastric fluid (pH=1.2). The developed method will allow quantitative determination of fosinopril sodium in orodispersible tablets that are to be developed. When designing orally disintegrating tablets, it is important to prevent the release of the active pharmaceutical ingredient into the oral cavity, thus avoiding the perception of its bitter taste, and to ensure that its release occurs directly into the gastric environment, especially when the formulation is intended for children.
Materials and methodsInstruments
UV-Visible (UV-VIS) Spectrophotometer Evolution® 300 (EVO® 300) equipped with VisionPro Software, Thermo Fisher Scientific, USA.
Chemicals and pharmaceutical dosage forms
FOS is purchased by Alfa Aesar, Germany. NaCl, HCl, Na2HPO4, H3PO4, and KH2PO4 are purchased from Sigma-Aldrich, St. Louis, USA. Commercial tablets of FOS are purchased from a local pharmacy.
Solvents: Preparation of two different dissolution media
Enzyme-free simulated salivary fluid (SSF) – a buffer with a pH of 6.8, which is prepared with 2.38 g of Na2HPO4, 0.19 g of KH2PO4, 8.00 g of NaCl, distilled water up to 1000 mL, and the required amount of H3PO4 to obtain the desired pH.
Enzyme-free simulated gastric fluid (SGF) – medium with a pH of 1.2, which is prepared with 2.0 g of sodium chloride, 7 mL of hydrochloric acid, and distilled water up to 1000 mL for a 1 L buffer.
Development and validation of the UV-spectrophotometric method
For the quantification of FOS, we developed a UV-spectrophotometric method in two different media: enzyme-free simulated salivary fluid (SSF) with a pH of 6.8 and enzyme-free simulated gastric fluid (SGF) with a pH of 1.2. It is validated according to the ICH scientific guideline for validation of analytical procedures for the parameters of specificity, linearity, detection limit, determination limit, analytical working range, stability, repeatability, precision, accuracy, and analytical yield.[28] All results are calculated and documented using Microsoft Excel software.
Standard solutions preparation
A quantity of 10 mg of FOS is accurately weighed and dissolved in 100 mL of pH 6.8 phosphate buffer (SSF) and pH 1.2 hydrochloric acid buffer (SGF) to prepare primary stock solutions with a concentration of 100 µg/mL. From these stock solutions, working standard solutions with concentrations of 2.5, 5, 10, 15, 20, 25, 50, and 75 µg/mL are prepared by serial dilution. The UV absorbance of each solution is subsequently measured using an Evolution™ 300 UV-Visible spectrophotometer (Thermo Scientific).
Specificity
To determine the wavelength of maximum absorption (λmax) of FOS, standard solutions with concentrations of 10, 15, 20, and 25 µg/mL are prepared in two dissolution media: SSF (pH 6.8) (Fig. 1) and SGF (pH 1.2) (Fig. 2). The UV absorbance spectra of these solutions are measured over the wavelength range of 200–300 nm using a UV-Visible spectrophotometer.
2D4417CD-38D5-53E1-B3CB-8F4D1738859B
UV spectrogram of standard solutions of FOS in SSF (pH 6.8), λmax=209 nm.
https://binary.pensoft.net/fig/1547944Linearity
Sixfold absorbance measurements (n=6) are performed for standard solutions of FOS at concentrations of 2.5, 5, 10, 15, 20, 25, 50, 75, and 100 µg/mL. The mean absorbance values are plotted against the corresponding concentrations to generate a standard curve, from which a calibration curve is established.
Limit of detection (LOD) and limit of quantification (LOQ)
The detection limit (LOD) and quantification limit (LOQ) are calculated using the standard deviation of the response of the blank (σ) and the slope of the calibration curve (S) according to ICH guidelines (ICH, 1995A; ICH, 1995B)[28]
LOQ = 10×(standard deviation of the response of the blank / slope of the calibration curve), or LOQ = 10×(σ/S)
LOD = 3.3×(standard deviation of the response of the blank / slope of the calibration curve), or LOD = 3.3×(σ/S)
In these formulas, σ is the SD of the analytical background response of the blank, and S is the slope of the calibration curve.
Analytical range
The lower limit of the analytical working range is determined as the established LOQ of the blank sample. The upper limit of the analytical working range is determined based on the linearity of the FOS calibration curve.
Stability
To determine the parameter stability of the standard solutions of FOS, three standard solutions with concentrations of 5.0, 10.0, and 15.0 µg/mL are selected, whose absorbances are measured 3 times in 4 different time intervals within 24 hours.
Repeatability and precision
Precision of the assay is assessed through repeatability (intra-day precision) and intermediate precision (inter-day variability).
Precision: the study is carried out at three different concentration levels (5, 10, 20 µg/mL) in SSF and SGF; each concentration is prepared in triplicate for FOS. The absorbance is measured at 209 nm in SSF and 207 nm for SGF. The results of the statistical analysis of precision are reported in terms of relative standard deviation (RSD).
In repeatability testing, RSD represents the variability among replicate samples prepared in parallel, analyzed by the same analyst, under identical experimental conditions, and within a single day.
In intermediate precision testing, RSD reflects the variability among independently prepared samples, which are analyzed on three different days by different analysts, thereby accounting for inter-day and inter-analyst variability.
Accuracy
The accuracy is assessed using the analytical recovery method using a standard addition: 1 mL of a standard solution with a concentration of 25, 50, and 100 µg/mL is added to a sample of known concentration. The analytical recovery is calculated using the formula:
(%) = (Ct – Co)/Cs×100,
where Ct is the total concentration of the drug after addition of the standard solution, Cs is the concentration of the drug in the sample, and Co is the concentration of the added standard solution.
Determination of FOS in commercial tablets
Ten tablets of commercial product X (10 mg nominal mass) are weighed and finely powdered. Five tablets of commercial product XX (20 mg nominal mass) are weighed and powdered, too. They are transferred separately into 100 mL volumetric flasks, and dissolution media of SSF and SGF, respectively, and added to a volume of 100 mL. From this stock solution with a concentration of 1 mg/mL, working solutions are obtained, whose absorbance is measured, and the amount of drug is calculated using the calibration curve equation. The solutions are prepared in triplicate from each commercial product.[29]
Results and discussion
We found an absorption maximum of FOS at λ=209 nm in SSF (Fig. 2) and an absorption maximum of FOS at λ=207 nm in SGF (Fig. 3).
C832029A-9B5B-585D-A28A-5CA33DBA8A13
UV spectrogram of standard solutions of FOS in SGF (pH 1.2), λmax=207 nm.
https://binary.pensoft.net/fig/1547945
Two primary standard solutions of FOS are prepared in SSF (pH 6.8) and SGF (pH 1.2), each at a concentration of 100 µg/mL. From these stock solutions, a series of working standard solutions with concentrations of 2.5, 5, 10, 15, 20, 25, 50, and 75 µg/mL is obtained by serial dilution. The mean absorbance values are plotted against concentration (µg/mL) for graphical representation of the absorbance/concentration relationship (Figs 4, 5), and calibration curves are constructed (Figs 6, 7).
E3BDBCE0-CE55-57DA-9125-52B1DF68BB3C
Graphical representation of the absorbance/concentration relationship of FOS in SSF, pH=6.8.
Calibration curve of FOS in SGF, pH=1.2, R2=0.9996.
https://binary.pensoft.net/fig/1547949
Linearity is assessed by constructing a calibration curve and determining the correlation coefficient (R²) using linear regression analysis.[30] The concentration range over which a linear relationship is observed was also documented. The calibration curves of FOS in SSF and SGF show very high correlation (R2=0.9996 at pH=6.8 and R2=0.9996 at pH=1.2).
LOQ and LOD
LOD and LOQ are two important characteristics in validation. LOD and LOQ are terms used to describe the smallest concentration that can be reliably measured by an analytical procedure.[31]
Three measurements are performed on three separate samples, replacing the real sample with the corresponding buffer, measuring the absorbance, and obtaining the following results for SSF with pH=6.8 (Table 1).
Results for determination of LOQ, pH=6.8, (n=3)
Measurement
Absorbance
1
0.003
2
0.004
3
0.003
Mean value, х
0.003333
Standard deviation, S(x)
0.000577
LOQ = (S(x)/0.0435)×10=0.133 µg/mL, where 0.0435 in the equation is the slope of the calibration curve. LOQ for SSF (pH=6.8) is 0.133 µg/mL.
The same test is repeated for SGF with pH 1.2, the data are presented in Table 2.
Results for determination of LOQ, pH=1.2, (n=3)
Measurement
Absorbance
1
0.005
2
0.006
3
0.004
Mean value, х
0.005
Standard deviation, S(x)
0.001
LOQ=(S(x)/0.0462)×10=0.216 µg/mL, where 0.0462 in the equation is the slope of the calibration curve. LOQ for SGF (pH=1.2) is 0.216 µg/mL.
The results for the limit of detection (LOD) show that (Table 3):
Results for LOD and LOQ
Media
LOQ
LOD
SSF pH 6.8
0.133 µg/ml
0.0438 µg/ml
SGF pH 1.2
0.216 µg/ml
0.0714 µg/ml
SSF: simulated salivary fluid; SGF: simulated gastric fluid; LOQ: limit of quantification; LOD: limit of detection
Stability of standard solutions of FOS in SSF (pH=6.8)
Concentration µg/mL
Measurements
Mean absorbance
SD
RSD %
5.0
12
0.206
0.004
2.123
10.0
12
0.413
0.009
2.278
15.0
12
0.630
0.005
0.824
Stability of standard solutions of FOS in SGF (pH=1.2)
Concentration µg/mL
Measurements
Mean absorbance
SD
RSD %
5.0
12
0.231
0.007
2.969
10.0
12
0.470
0.005
1.116
15.0
12
0.686
0.001
0.182
LOD=(S(x)/0.0435)×3.3 for SSF (рН=6.8) is 0.0438 µg/mL.
LOD=(S(x)/0.0462)×3.3 for SGF (рН=1.2) is 0.0714 µg/mL.
Analytical range
The working concentration range is determined based on the linearity of the calibration curves, as well as the calculated LOQ for two different buffer media – SSF and SGF:
The analytical range in phosphate buffer SSF (pH 6.8) is from 0.133 up to 20 µg/mL.
The analytical range in the hydrochloric acid buffer SGF (pH 1.2) is from 0.216 to 20 µg/mL.
Stability
The results for stability of standard solutions of FOS are presented in Table 4 for SSF and in Table 5 for SGF.
Repeatability and precision
Results of repeatability and intermediate precision of the method are presented in Table 6. The precision of an analytical method refers to the consistency of results obtained from repeated measurements of the same sample under specified conditions.[32]
Repeatability and intermediate precision of the analysis (n=3 for each individual concentration)
Dissolution media
Standard solutions concentration
Repeatability (Intra-day)
Intermediate precision (Inter-day)
Mean absorbance ±SD
RSD %
Mean absorbance ±SD
RSD %
рН 6.8
5 µg/mL
0.209±0.004
1.891
0.211±0.003
1.388
10 µg/mL
0.428±0.005
1.214
0.430±0.005
1.166
20 µg/mL
0.854± 0.005
0.569
0.855±0.005
0.541
рН 1.2
5 µg/mL
0.229±0.003
1.152
0.229±0.002
0.731
10 µg/mL
0.470±0.005
1.125
0.471±0.006
1.175
20 µg/mL
0.928±0.006
0.616
0.927±0.005
0.533
The sample concentration is calculated using the calibration curve equations for the two different dissolution media. The RSD (%) value in repeatability and precision studies is less than 2% indicating that the method is precise.
Accuracy
For the validation of a UV-spectrophotometric method, accuracy is evaluated through recovery studies by adding known quantities of FOS reference standard into the samples at the start of the analytical procedure.[19] Accuracy refers to the compliance between the measured values and the true value and was determined by comparing the found amount with the added amount. The percentage of recovery and relative standard deviation are calculated and presented in Table 7.
Evaluating the accuracy of the UV-spectrophotometric method by analytical yield
Sample content µg n=3
Added 1 mL standard solution µg/mL
Quantitative content µg
Accuracy (analytical yield) %
SD
RSD %
SSF pH 6.8
98.5±0.007
100
199.1±0.5
100.3
0.5
0.261
50
149.3±0.6
99.8
0.5
0.345
25
124.8±0.8
100.3
0.6
0.514
Standard accuracy %
100.1
0.6
0.373
SGF pH 1.2
98.7±0.005
100
199.0±0.4
100.1
0.3
0.148
50
148.4±0.5
99.6
0.5
0.331
25
123.9±0.2
100.0
0.2
0.132
Standard accuracy %
99.9
0.3
0.203
RSD (%) value in accuracy studies is 0.373 for SSF and 0.203 for SGF (under 2%), and the accuracy degree ranges between 99 and 100%, proving that the proposed method is accurate.
Determination of FOS in pharmaceutical formulations
The developed UV-spectrophotometric method is used for an experimental study of the quantitative content of FOS in commercial tablets, which are authorized by the Bulgarian Drug Agency (BDA) for use in the Republic of Bulgaria. The results are presented in Table 8.
Assay of commercial pharmaceutical formulations
Commercial tablets, Label claim mg
Amount obtained % ± SD
рН 6.8
рН 1.2
Product X 10 mg
98.9%±0.008
99.8%±0.098
Product XX 20 mg
99.1%±0.089
99.7%±0.066
The results show that the developed UV-spectrophotometric method enables rapid and straightforward quantification of FOS in commercial tablet formulations, eliminating the need for labor-intensive sample preparation. Additionally, the method relies on simple instrumentation, offering a more accessible alternative to complex analytical techniques.[19]
Conclusions
A UV-spectrophotometric analytical method is developed and validated for the quantitative determination of FOS in enzyme-free simulated salivary fluid and enzyme-free simulated gastric fluid. The developed method is suitable for the quantification of FOS in both bulk substances and commercial pharmaceutical formulations. The experimental data confirm the method’s suitability and reliability for the quantitative analysis of FOS in solid pharmaceutical dosage forms. Furthermore, the method is rapid and cost-effective compared to techniques such as HPLC. It is characterized by simplicity, reproducibility, and sensitivity, providing acceptable accuracy and precision.[33]
Ethical approval
Not applicable
Ethical statements
The author declared that no clinical trials were used in the present study.
The author declared that no experiments on humans or human tissues were performed for the present study.
The author declared that no informed consent was obtained from the humans, donors or donors’ representatives participating in the study.
The author declared that no experiments on animals were performed for the present study.
The author declared that no commercially available immortalized human and animal cell lines were used in the present study.
Conflict of interest
The author has declared that no competing interests exist.
Use of AI
No use of AI was reported.
Funding
The study was funded by the European Union through the ‘Research, Innovation, and Digitalization for Smart Transformation’ 2021–2027 program.
Data availability
All data used are referenced or included in the article.
Author contributions
The author is solely responsible for the conceptualization, methodology, software, validation, formal analysis, investigation, resources, data curation, writing–original draft preparation, writing–review and editing, visualization, and supervision of the article.
Acknowledgments
The author gratefully acknowledges the financial support of Project BG16RFPR002-1.014-0007, ‘Center for Competence PERIMED-2’. funded by the European Union through the ‘Research, Innovation, and Digitalization for Smart Transformation’ 2021–2027 program.
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