Development, validation and comparison of NIR and Raman methods for the identification and assay of poor-quality oral quinine drops

doi:10.1016/j.jpba.2015.02.049

Journal of Pharmaceutical and Biomedical Analysis

Volume 111, 10 July 2015, Pages 21-27

https://doi.org/10.1016/j.jpba.2015.02.049 Get rights and content

Highlights

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The oral quinine drops were prepared.
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Raman and NIR spectroscopy methods were developed and validated.
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The methods were applied for analysis the real and substandard drugs.
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The real samples were collected on the Congolese pharmaceutical market.

Abstract

Poor quality antimalarial drugs are one of the public's major health problems in Africa. The depth of this problem may be explained in part by the lack of effective enforcement and the lack of efficient local drug analysis laboratories. To tackle part of this issue, two spectroscopic methods with the ability to detect and to quantify quinine dihydrochloride in children's oral drops formulations were developed and validated. Raman and near infrared (NIR) spectroscopy were selected for the drug analysis due to their low cost, non-destructive and rapid characteristics. Both of the methods developed were successfully validated using the total error approach in the range of 50–150% of the target concentration (20% W/V) within the 10% acceptance limits. Samples collected on the Congolese pharmaceutical market were analyzed by both techniques to detect potentially substandard drugs. After a comparison of the analytical performance of both methods, it has been decided to implement the method based on NIR spectroscopy to perform the routine analysis of quinine oral drop samples in the Quality Control Laboratory of Drugs at the University of Kinshasa (DRC).

Graphical abstract

Introduction

Malaria remains one of the most rampant illnesses worldwide and is one of the main causes of child mortality in developing countries [1], [2]. The treatment of uncomplicated malaria is based on conventional antimalarial drugs (e.g. chloroquine, artemisinin derivatives, atovaquone, etc.). These drugs are essentially used as combinations due to the growing resistance observed with single-drug therapy [3]. However, quinine is still recommended alone in the treatment of severe and/or cerebral malaria attacks as well as for chloroquine-resistant falciparum malaria [4]. Four quinine based dosage forms are found on the pharmaceutical market in DRC: tablets (250 and 500 mg), ampuls (250 and 500 mg/2 mL), syrup (100 mg/mL) and oral drops (200 mg/mL). The last three dosage forms are the most used with 0–5 year old children. In 2009, the Health Ministry of the DRC warned citizens against quinine oral drops “Quinizen 20%” that were found to have been counterfeit and substandard [5].

Poor quality (substandard, counterfeit and degraded) or substandard/spurious/falsely-labelled/falsified/counterfeit anti-malarial drugs constitute a major public health concern especially in developing countries where the pharmaceutical market is poorly regulated and controlled [6]. It has been estimated that at least a third of the drugs sold in Africa are fake. The use such drugs may lead to therapeutic failure, death and reinforce drug resistance [7], [8].

Vibrational spectroscopic techniques, such as near infrared (NIR) and Raman spectroscopies are frequently used techniques in the field of quantitative drug analysis [9], [10], [11] and in the fight against counterfeit drugs [12], [13], [14], [15]. These techniques have the advantages of being non-destructive, fast, requiring little or no sample preparation, as well as being environmental friendly [16]. The foremost advantage for drug analysis in developing countries however is their low cost in routine analysis and the absence of consumables.

The aim of the present research was to develop NIR and Raman methods able to detect and to quantify quinine in 20% (W/V) oral drops solutions from a Congolese drug-manufacturing laboratory (manufacturer A). These methods were fully validated by the “total error” approach [17], compared by mean of a Bland and Altman analysis [18] and then tested on samples from several manufacturers.

Section snippets

Reagents

Ammonium formate (98.1%), hydrochloric acid (37%), and methanol (HPLC gradient grade) were purchased from Merck (Darmstadt, Germany). Benzoic acid and propylene glycol were purchased from Sigma–Aldrich (Saint-Louis, MO, USA). The reference standard of quinine dihydrochloride (100.8%) for the HPLC analysis was purchased from Molekula Ltd. (Dorset, UK). Ultrapure water was obtained from a Milli-Q Plus 185 water purification system (Millipore, Billerica, MA, USA).

NIR equipment

The oral drop samples were

Validation of the reference method

The method was successfully validated using the “total error” approach in the range of 50–150 μg mL⁻¹ with acceptance limits set at 10% according to the USP for quinine sulphate tablet assay [21]. Trueness, precision (repeatability and intermediate precision), accuracy and linearity of the method were found to be acceptable (see also Table 1).

Quantitative NIR study

Quantifying an API in an aqueous matrix may be a difficult task with NIR spectroscopy. Indeed, the matrix absorbance spectrum shows that the multiple

Conclusion

The main objective of this study was to develop and validate efficient, rapid and cost-effective analytical methods for the analysis of quinine dihydrochloride 20% (W/V) presented as an oral drop formulation manufactured and marketed in the DRC.

To meet these requirements, NIR and Raman spectroscopic methods were successfully developed and validated using the total error approach with acceptance limits fixed at 10% in the range of 50–150% of the target concentration. A comparison of the two

Acknowledgments

The authors are deeply grateful to the Belgian “Commission de la Coopération au Développement” for financially supporting J.K. Mbinze’ and to the New Cesamex and AV Pharma laboratories for collaboration. Walloon Region of Belgium is also gratefully acknowledged for P.-Y. Sacré funding (convention N° 1117469).

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¹: These authors have equally contributed to this article.

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Short communicationDevelopment, validation and comparison of NIR and Raman methods for the identification and assay of poor-quality oral quinine drops

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Reagents

NIR equipment

Validation of the reference method

Quantitative NIR study

Conclusion

Acknowledgments

J. Chromatogr. A

Lancet Infect. Dis.

J. Pharm. Biomed. Anal.

Anal. Chim. Acta

Chemom. Intell. Lab. Syst.

TrAC Trends Anal. Chem.

J. Pharm. Biomed. Anal.

J. Pharm. Biomed. Anal.

J. Pharm. Biomed. Anal.

J. Pharm. Biomed. Anal.

Short communication
Development, validation and comparison of NIR and Raman methods for the identification and assay of poor-quality oral quinine drops