A chromatographic approach to development of 5-aminosalicylate/folic acid fixed-dose combinations for treatment of Crohn’s disease and ulcerative colitis

AbstractMedication adherence is an important factor in inflammatory bowel disease therapy, which includes regular supplementation of malabsorbed vitamins. Absorption of folic acid is limited due to the damaging of the gastrointestinal tract, which can increase the chances to develop megaloblastic anaemia and colorectal cancer. In this work, 5-aminosalicylates (mesalazine, balsalazide, sulfasalazine and olsalazine) and folic acid were characterized regarding their pharmacokinetic related properties (hydrophobicity, phospholipid and plasma protein binding) using the biomimetic chromatographic approach. Despite the high binding percentage of 5-aminosalicylates for human serum albumin (> 61.44%), results have shown that folic acid binding to human serum albumin protein is far greater (69.40%) compared to α1-acid-glycoprotein (3.45%). Frontal analysis and zonal elution studies were conducted to provide an insight into the binding of folic acid to human serum albumin and potential competition with 5-aminosalicylates. The analytical method for the simultaneous determination of assay in proposed fixed-dose combinations was developed and validated according to ICH Q2 (R1) and FDA method validation guidelines. Separation of all compounds was achieved within 16 min with satisfactory resolution (Rs > 3.67) using the XBridge Phenyl column (150 × 4.6 mm, 3.5 µm). High linearity (r > 0.9997) and precision (RSD < 2.29%) was obtained, whilst all recoveries were within the regulatory defined range by British (100.0 ± 5.0%) and United States Pharmacopeia (100.0 ± 10.0%).

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Chemometrics-assisted multi-instrumental techniques for investigation of interactions of dapagliflozin with normal and glycated human serum albumin: Application to exploiting second-order advantage for determination of glycated human serum albumin as a biomarker for controlling diabetes

Microchemical Journal ◽

10.1016/j.microc.2021.106313 ◽

2021 ◽

Vol 167 ◽

pp. 106313

Author(s):

Asma Mohamady ◽

Mohsen Shahlaei ◽

Vali Akbari ◽

Hector C. Goicoechea ◽

Ali R. Jalalvand

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Second Order

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Simultaneous Determination of Human Serum Albumin and Low-Molecular-Weight Thiols after Derivatization with Monobromobimane

Molecules ◽

10.3390/molecules26113321 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3321

Author(s):

Katarzyna Kurpet ◽

Rafał Głowacki ◽

Grażyna Chwatko

Keyword(s):

Molecular Weight ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Simultaneous Determination ◽

Reversed Phase ◽

Fluorescence Labeling ◽

Detector Response ◽

Low Molecular Weight

Biothiols are extremely powerful antioxidants that protect cells against the effects of oxidative stress. They are also considered relevant disease biomarkers, specifically risk factors for cardiovascular disease. In this paper, a new procedure for the simultaneous determination of human serum albumin and low-molecular-weight thiols in plasma is described. The method is based on the pre-column derivatization of analytes with a thiol-specific fluorescence labeling reagent, monobromobimane, followed by separation and quantification through reversed-phase high-performance liquid chromatography with fluorescence detection (excitation, 378 nm; emission, 492 nm). Prior to the derivatization step, the oxidized thiols are converted to their reduced forms by reductive cleavage with sodium borohydride. Linearity in the detector response for total thiols was observed in the following ranges: 1.76–30.0 mg mL−1 for human serum albumin, 0.29–5.0 nmol mL−1 for α-lipoic acid, 1.16–35 nmol mL−1 for glutathione, 9.83–450.0 nmol mL−1 for cysteine, 0.55–40.0 nmol mL−1 for homocysteine, 0.34–50.0 nmol mL−1 for N-acetyl-L-cysteine, and 1.45–45.0 nmol mL−1 for cysteinylglycine. Recovery values of 85.16–119.48% were recorded for all the analytes. The developed method is sensitive, repeatable, and linear within the expected ranges of total thiols. The devised procedure can be applied to plasma samples to monitor biochemical processes in various pathophysiological states.

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