| dc.description.abstract | Pain is a common menace afflicting many people worldwide. There are a myriad of
medications that are available commercially to combat all forms of pain. The quality of
medicines is an important aspect in healthcare provision. However, more focus is put on
the quality of drugs for the major diseases such as tuberculosis, HIV/AIDS and malaria
than for analgesics. There is little quality surveillance of the pain medications that are
available commercially in Kenya. There are no official methods for the simultaneous
analysis of most of the drug compounds present in the commonly available pain
medications. Only the methods for the analysis of paracetamol and caffeine preparations
and paracetamol and codeine phosphate preparations are available. This makes the
analysis of samples expensive and time consuming as each component would be analyzed
individually.
In the present study, a simple, rapid, precise, sensitive and robust isocratic elution
reversed-phase liquid chromatographic method was developed for the simultaneous
determination of caffeine, chlorzoxazone, codeine, diclofenac, doxylamine, ibuprofen and
paracetamol. These seven compounds are present in some commonly available
formulations used for pain management in Kenya.
A mixture of these seven compounds was separated using a liquid chromatographic
system with a mobile phase consisting of methanol-0.25 M sodium octanesulfonate-0.2
M ammonium acetate pH 6.5-water (50:2:10:38, % v/v/v/v). This was delivered at a flow
rate of 1 mUmin through a column with the dimensions 250 mm in length and 4.6 mm
internal diameter packed with an octyldecylsilane stationary reverse phase (Phenomenex
Gemini® 511, CIS) maintained at a temperature of 40°C using a column oven and a UV
detection wavelength of 220 nm.
Validation of the method demonstrated that the limit of detection for caffeine,
chlorzoxazone, codeine, diclofenac, doxylamine, ibuprofen and paracetamol were 11.99
ng, 20.72 ng, 25.08 ng, 12.50 ng, 32.93 ng, 12.02 ng, 22.36 ng, and the limit of
quantitation were 79.92 ng, 103.60 ng, 104.50 ng, 62.49 ng, 164.64 ng, 48.08 ng, 111.80
Xlll
ng respectively. The method was accurate with recovery rates of 100.3% (caffeine),
101.6% (chlorzoxazone), 98.3% (codeine), 98.1% (diclofenac), 102.7% (doxylamine),
99.2% (ibuprofen) and 98.1% (paracetamol). The method was linear over a concentration
range of 75% to 125% for all seven compounds with the respective coefficient of
determination (R2) values being 0.9995 (caffeine), 0.9986 (chlorzoxazone), 0.9992
(codeine), 0.9993 (diclofenac), 0.9975 (doxylamine), 0.9998 (ibuprofen) and 0.9960
(paracetamol). The method also demonstrated adequate intra-day and intermediate
precision with intra-day precision coefficients of variation ranging from 0.15-0.37% and
intermediate precision coefficients of variation ranging from 0.91-1. 96% for the seven
compounds.
The method developed was used for the analysis of four randomly selected commercially
available pain medications containing varying combinations of the seven compounds.
Three batches of each of the drug samples were analyzed and the results obtained
demonstrated that there was minimal batch variation. The assay values for caffeine,
chlorzoxazone, diclofenac and ibuprofen ranged from 95.3-102%, 92.0-96.6%, 95.5-
98.6% and 96.7-99.3% respectively. The assay values of paracetamol ranged from 99.6-
117%. One product was found to have values of paracetamol consistently higher than the
adopted limits with assay values ranging from 115-117%. The levels of codeine and
doxylamine were found to be consistently below the adopted specifications with assay
values ranging from 51.3-53.2% and 65.2- 67.2% respectively.
The method can be used in the analysis of pain medications containing any combination
of the seven compounds and it can therefore be adopted by quality control laboratories
for routine analysis and in the post market surveillance of pain medications. | en |
| dc.description.department | a
Department of Psychiatry, University of Nairobi, ; bDepartment of Mental Health, School of Medicine,
Moi University, Eldoret, Kenya | |
