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Fluorescence spectroscopy has an important role in the determination of very small quantities of substances, especially in biological fluids. For this reason, most analysts have adopted the use of this technique in their biological studies and research, which helps them in the determination of any substance found in trace amounts. In addition to the high sensitivity of the fluorimetric technique, it has the advantages of simplicity and being green for the environment. All these reasons encourage the use of fluorimetric spectroscopy for quantifying co-administered therapy in biological fluids, which is considered a crucial step for patients, particularly in emergent cases requiring monitoring of administered therapeutic drugs. In this work, a sensitive, simple, economic, and environmentally friendly fluorimetric analytical technique was developed for the simultaneous determination of prucalopride succinate (a novel anti-constipation agent) and empagliflozin (an anti-diabetic agent) in pharmaceutical forms and spiked plasma depending on third-derivative signal processing at 333 and 314 nm, respectively. Conventional fluorescence spectra of both drugs showed a large overlap that hindered their simultaneous determination. So, third-order derivative fluorescence was adopted to overcome this overlap. The third-derivative corresponding to each spectrum was recorded using data points = 17 and a scaling factor of 10. The greenness of the proposed method was evaluated using an eco-scale scoring system, revealing excellent greenness. Analytical method parameters were validated following ICH guidelines. The method showed high sensitivity, covering a concentration range of 50-1100 ng/mL and 4-500 ng/mL for empagliflozin and prucalopride, respectively, allowing the pharmacokinetic study of both drugs in biological fluids. The LOD values were 14.09 and 0.91 ng/mL, while the LOQ values were 42.72 and 2.77 ng/mL for empagliflozin and prucalopride, respectively.

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An economical & eco-friendly spectrofluorometric method has been developed for the determination of prucalopride succinate (PRU) in human urine on the basis of the drug's native fluorescence. The type of solvent and the wavelengths of excitation and emission have been carefully selected for optimal experimental conditions. In deionized water, the fluorescence intensity was measured at λ emission 362 nm upon excitation at 310 nm. This bio-validated method was carried out using 30uL urine without any preliminary steps. The calibration curve for prucalopride succinate shows a linear relationship in a concentration range of 0.75-5.5 µg/mL. Accuracy and precision were obtained using 4 quality control samples which are: 0.75 µg/ mL (LLOQ), 2.25 µg/mL (QCL), 2.5 µg/mL (QCM) & 4.125 µg/mL (QCH). The validation of this proposed technique obeys European Medicines Agency (EMA) Guidelines for validating bioanalytical methods and the greenness assessment was evaluated according to the Analytical GAPI approach.

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A highly sensitive spectrofluorimetric method is developed for the determination of prucalopride succinate (PRU). The method depends on lanthanide-sensitized luminescence due to complex formation between the drug and terbium chloride (Tb+3) which is enhanced by the addition of 8 hydroxyquinoline (8HQ) and phosphate buffer (0.02 M, pH 3.2). The calibration curve was constructed over the linear range 10-300 ng/mL after excitation at 226 nm and measuring the emission of the ternary complex at 544 nm. The method was validated according to ICH Q2 (R1) guidelines and showed a good recovery ± RSD of 100.41% ± 1.26, the limits of detection and quantitation were found to be 2.81 and 8.53 ng/mL, respectively. The proposed method was successfully applied for the determination of the drug marketed tablet dosage form and the results were in good agreement with the reference method. Also, the method greenness was evaluated according to Complex-GAPI and analytical Eco-Scale.

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Objective To compare the short-term curative effects of prucalopride and mosapride respectively combined with low dose polyethylene glycol in treating elderly refractory functional constipation.Methods Ninety patients with elderly refractory functional constipation in the outpatient department of our hospital from May 2014 to February 2016 were retrospectively analyzed and divided into two groups randomly,45 cases in each group.the prucalopride group:Prucalopride Succinate Tablets,2mg,4 times daily;the mosapride group:Mosapride Citrate Capsules,5mg,3 times daily.Polyethylene Glycol Electrolytes Powder(PEG) was also used in the two groups,13.125g,twice daily.The course of treatment was 4 weeks.The first defecating time and defecation difficulty relief time,average weekly spontaneous complete bowel movements (SCBM),defecating difficulty,stool character,adverse reactions and change of life quality were observed in the two groups.Results The treatment effective rate of slow transit constipation(STC) and defecatory disorder had the statistical difference between the two groups (P0.05).Compared with the mosapride group,the first defecating time and defecation difficulty relief time in the prucalopride group were shorter with statistical difference (P0.05).The total effective rate had statistical difference between the two groups(P<0.05).The incidence rate of adverse reactions had no statistical difference between the two groups(17.78% vs.15.56%,P<0.05).The total average score of PAC-QOL after treatment in the two groups were both decreased,moreover the decrease in the prucalopride group was more obvious;the difference between the two groups had statistical significance(P<0.05).Conclusion Prucalopride +PEG take effect faster in the treatment of elderly refractory functional constipation and has the advantages in the aspects of overall curative effect and life quality improvement,which is specially suitable for STC and defecatory disorder type.

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Objective To observe the therapeutic effect of Baizhu Shengjiang Decoction combined with Prucalopride Succinate Tablets for chronic functional constipation. Methods Sixty patients with chronic functional constipation were randomly divided into treatment group and control group, 30 cases in each group. The treatment group was treated with Baizhu Shengjiang Decoction combined with Prucalopride Succinate Tablets orally, and the control group was treated with oral administration of Prucalopride Succinate Tablets alone. The therapeutic effects on traditional Chinese medicine (TCM) symptoms and constipation, and the follow-up therapeutic effect of the two groups were evaluated after treatment. During the three months after the completion of treatment course, the recurrence of constipation was monitored. Results (1) The cure rate of the treatment group was 90.0％ and that of the control group was 60.0％, indicating that the therapeutic effect on TCM symptoms in the treatment group was stronger than that of the control group(P < 0.05).(2) In respect of the relief of constipation, the markedly effective rate was 93.3％ in the treatment group and was 50.0％ in the control group, and the overall effective rate was 100.0％ in the treatment group and was 73.3％ in the control group, the difference being significant between the two groups(P<0.05 or P<0.01).(3) During the treatment, the percentage of patients with weekly completely spontaneous defecation frequency ≥3 was 86.7％ in the treatment group, and was 53.3％ in the control group, the difference being significant (P < 0.05). (4) The results of 3-month follow-up after the completion of treatment course showed that one case from the treatment group had the recurrence of constipation, and the recurred cases from the control group were 6, the difference being significant (P < 0.05). Conclusion Oral use of Baizhu Shengjiang Decoction combined with Prucalopride Succinate Tablets exerts certain therapeutic effect for chronic functional constipation, which is effective both on relieving constipation symptoms and on reducing recurrence rate.

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Mosapride, a gastrointestinal prokinetic drug, is an agonist of 5-hydroxytryptamine (5-HT) receptor 4 that also reduces blood glucose. Whether 5-HT4 receptor is distributed in pancreatic islets and whether mosapride can directly stimulate insulin secretion is unclear. In the present study, the protein expression and cellular location of 5-HT4 receptor in pancreas was detected through western blotting and immunofluorescence. The acute effects of 5-HT4 receptor agonists, mosapride and prucalopride, on insulin secretion were investigated in vivo and in vitro in normal and alloxan-induced diabetes rats. The results indicated that 5-HT4 receptor immunoreactivity was co-existed in the islets insulin-immunoreactive cells of rat, mouse, pig and human. However the immunoreactive cells of insulin and 5-HT4 receptor and the protein expression of 5-HT4 receptor were significantly decreased in the pancreas of alloxan-induced diabetes rats. In normal rats, mosapride and prucalopride decreased blood glucose and increased insulin secretion during glucose tolerance test, in association with an increase in glucose-stimulated insulin secretion, which was abolished by the 5-HT4 receptor antagonist GR113808. In diabetes rats, mosapride and prucalopride failed to improve blood glucose and insulin levels in the group of 180mg/kg alloxan, but increased glucose-stimulated insulin secretion in the group of 120mg/kg alloxan in vitro. We conclude that 5-HT4 receptor is distributed in the islet ß cell. Activation of 5-HT4 receptor is able to stimulate insulin secretion directly, thereby reduce blood glucose. The study provides important experimental evidences for the 5-HT4 receptor regulating insulin secretion and acting as a potential drug target in diabetes treatment.

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The present study reports the degradation behaviour of a new prokinetic agent, Prucalopride succinate, under various stress conditions as per International Conference on Harmonization guidelines (ICH, Q1A (R2)). The investigation involved monitoring decomposition of the drug under hydrolytic (acidic, basic and neutral), oxidative, photolytic and thermal stress conditions followed by characterization of the degradation products (DPs) and process related impurities (IMPs). A rapid, precise, accurate and robust reverse phase high performance liquid chromatography (RP-HPLC) method has been developed involving mobile phase of 20mM ammonium bicarbonate buffer and acetonitrile: methanol (80:20v/v) on a Waters Xbridge-C8 (150mm×4.6mm i.d., 3.5µm) column using gradient elution. The drug was found to be degraded in hydrolytic (acidic) and oxidative conditions, whereas it was stable under basic and neutral hydrolytic, photolytic and thermal stress conditions. The method was extended to LC-ESI-QTOF-MS/MS for the structural characterization of DPs and process related IMPs. Structural characterization was carried out based on the generated molecular formula of DPs and its fragment ions. It has been observed that two major DPs were formed under each acid hydrolysis and oxidative stress conditions. The most probable mechanisms involved in the formation of DPs were also proposed. Finally, the method was validated in the term of specificity, linearity, accuracy, precision, and robustness as per ICH guidelines, Q2 (R1).

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