Quality of Glucosamine Products: Is it a Potential Reason for Inconsistent Clinical Outcomes in Osteoarthritis?

BACKGROUND: Clinical studies have reported inconsistent outcomes of glucosamine therapy in osteoarthritis patients. One possible reason could be the use of glucosamine products of varying quality. OBJECTIVE: Hence, this study aimed to assess the quality of glucosamine products marketed in Australia and India. This is the first study to investigate both the content and dissolution profiles of glucosamine products. METHOD: The content and dissolution analysis of Australian (n = 25 brands) and Indian (n = 21 brands) glucosamine products was performed according to the criteria specified in the United States Pharmacopoeia (USP). RESULTS: The quality analysis revealed that 16% and 18% of Australian brands, as well as 24% and 19% of Indian brands, did not fulfil the USP content and dissolution criteria, respectively. In approximately half of these cases, the glucosamine content was only slightly below (<3%) that specified by the USP and dissolution was achieved within 15 min after the duration specified by the USP. CONCLUSIONS: The majority of the brands did meet both the content and dissolution analysis criteria of the USP. The extent of deviation from the specified criteria for the other brands was probably insufficient to account for the significant variability in clinical effects. Hence, the study proposed that inter-patient pharmacokinetic variations in glucosamine could be another potential reason for inconsistent therapeutic effects.

Variation in the pharmacokinetics of glucosamine in healthy individuals.

OBJECTIVES: Clinical trial data for the efficacy of glucosamine in OA are conflicting. Reportedly, Rotta-manufactured glucosamine products are more likely to be effective, and a possible explanation is greater bioavailability than other brands. Specifically, the aim was to compare the steady-state pharmacokinetics of Rotta- and non-Rotta-manufactured glucosamine products in healthy volunteers and examine the interindividual variability. METHODS: In a crossover design, healthy adult participants ingested 1500 mg/day of a Rotta (DONA powder sachets; imported by Mylan Health, Carole Park, QLD, Australia) and a non-Rotta (glucosamine sulphate 1500 mg one-a-day tablet; Blackmores, Warriewood, NSW, Australia) glucosamine product/brand individually for 6 days. Blood samples were collected immediately before and for 12 h after the ingestion of the last dose of each brand and analysed to determine plasma levels of glucosamine. The pharmacokinetic parameters at steady state [including the minimum (Css min) and maximum (Css max) plasma concentration of glucosamine, time to reach Css max post-dosing (Tss max) and area under the plasma concentration vs time curve (AUCss 0-12)] for each brand were calculated and statistically compared. RESULTS: Fourteen participants [mean age 35.5 years (s.d. 8.8)] were recruited (64.2% males). No significant differences were observed in the pharmacokinetic parameters between the two brands. However, for both brands, the coefficient of variation for Css min, Tss max and AUCss 0-12 exceeded 20%, indicating considerable differences in the parameters between participants. No significant association of the pharmacokinetic parameters was observed with various dosing- and participant-related variables. CONCLUSION: Substantial interindividual differences in the absorption and elimination of glucosamine could be a cause of variable clinical outcomes in OA. TRIAL REGISTRATION: The study was registered with the Australian New Zealand Clinical Trials Registry (http://www.ANZCTR.org.au/ACTRN12618000699268p.aspx), number ACTRN12618000699268p.

Variation in Plasma Levels of Glucosamine With Chronic Dosing: A Possible Reason for Inconsistent Clinical Outcomes in Osteoarthritis.

PURPOSE: Glucosamine is widely used by patients with osteoarthritis (OA) to provide symptomatic relief and to delay disease progression. However, clinical studies have reported inconsistent clinical outcomes. The current study hypothesized that the reported inconsistent clinical results could be, in part, due to variable bioavailability and elimination of glucosamine. This study therefore aimed to determine steady-state minimum plasma concentrations (Css min) of glucosamine to examine the variability among patients taking the supplement. METHODS: Patients with OA who had been taking glucosamine for at least 1 week were recruited. Patients' blood samples were collected 24 h after the ingestion of the previous dose to determine Observed Css min and after a 5-day washout period to determine the endogenous glucosamine levels (GlcNend). The Actual Css min was calculated by using the following equation: Actual Css min = Observed Css min - GlcNend. The glucosamine plasma concentrations were determined by using a previously developed HPLC method. FINDINGS: Ninety-one participants (age range, 42-89 years; mean [SD] age, 68.2 [7.6] years) were recruited (70% females). There was substantial (106-fold) variation, with a 45% coefficient of variation, between the Actual Css min levels (3-320 ng/mL) in participants. No significant association of Actual Css min was observed with various dose- and patient-related variables. IMPLICATIONS: The observed high variability in steady-state plasma concentrations indicates substantial inter-patient differences in the absorption and elimination of glucosamine, which could be a cause for inconsistent clinical outcomes in patients with OA.

A novel and sensitive HILIC-CAD method for glucosamine quantification in plasma and its application to a human pharmacokinetic study.

The clinical effect of glucosamine, the most widely used supplement in patients with osteoarthritis, on joint pain and function improvement, is reported to be inconsistent. Inter-patient variability in the pharmacokinetics of glucosamine, especially its oral absorption, could contribute to the inconsistent clinical outcomes. To test this hypothesis, a novel but simple Hydrophilic Interaction Liquid Chromatography coupled with Charged Aerosol Detector method was developed and validated. The sample was prepared by simple protein precipitation and analysed using an amino column and acetonitrile:100 mM ammonium formate with gradient elution. The developed method was linear (12.5-800 ng/mL, r2 = 0.999) and the relative standard deviations for intra- and inter-day accuracy, precision and repeatability were all less than 6%. The sensitivity of the method (lower limit of quantitation; 12.5 ng/mL) allowed the quantification of endogenous and exogenous glucosamine levels in 12 patients with osteoarthritis, taking 1500 mg glucosamine daily. The analysis showed 120-fold variation (81.7% variance) in exogenous glucosamine levels among the patients, indicating that substantial variability in the extent of absorption and/or rate of elimination could be a possible cause for the reported inconsistent clinical outcomes. The newly-developed method was sensitive and can be used to study the pharmacokinetics of glucosamine.

Development and validation of a novel high performance liquid chromatography-coupled with Corona charged aerosol detector method for quantification of glucosamine in dietary supplements.

INTRODUCTION: Glucosamine dietary supplements are commonly used for the management of osteoarthritis (OA). However, clinical trials have reported varying outcomes with regard to joint function and disease progression. One of the possible reasons for variability in observed effects of glucosamine could be that, unlike prescription drugs, the quality of manufactured dietary supplements is not closely monitored in many countries. Therefore, there is the possibility that the actual amount of glucosamine present in a dietary supplement is different from that claimed on the label. The quality control of glucosamine supplements is further complicated by the unavailability of a simple and effective analytical method for the analysis of glucosamine. Therefore, the aim of this study was to develop a simple analytical method that could be easily adapted by the pharmaceutical industry for routine analysis of glucosamine. AIMS: To develop a novel high-performance liquid chromatography (HPLC) method for the quantification of glucosamine, and determine the amount of glucosamine present in a sample of dietary supplements commercially available in Australia and India. METHODS: Chromatographic separation of glucosamine was achieved using a zwitter-ionic hydrophilic interaction liquid chromatography column with a mobile phase consisting of 60% acetonitrile and 40% of 85 mM ammonium acetate, at a flow rate of 0.3 mL/min and column temperature 40°C. The developed method was validated for intra- and inter-day linearity, accuracy, precision, and reproducibility. The newly-developed method was subsequently used to analyse 12 glucosamine supplements. RESULTS: The developed method was selective for glucosamine, which had a retention time of 5.9 min. The standard curve was linear with a correlation coefficient (r2) exceeding 0.99, over the range of 10-200 µg/mL for glucosamine. The relative standard deviations for intra- and inter-day accuracy, precision and reproducibility were all less than 4%. The amount of glucosamine determined in six Australian and six Indian glucosamine supplements ranged between 98.7-101.7% and 85.9-101.8% of the labelled values, respectively. DISCUSSION: Unlike previous HPLC methods, this newly-developed HPLC technique does not require pre-derivatisation and can separate glucosamine from both hydrochloride and sulphate salts, and from other amino sugars, such as chondroitin sulphate present in dietary supplements. This simple and effective technique can be employed by analytical laboratories for the quality control of glucosamine dietary supplements. CONCLUSION: The current study has developed a new analytical technique using HPLC-Corona CAD, which can analyse underivatised glucosamine hydrochloride and sulphate within 6 minutes. Using the novel assay, we confirmed that unlike the tested Australian dietary supplements, only half of the tested Indian products had a glucosamine content within ±10% of what was claimed on the label.