Colorimetric determination of olanzapine via charge-transfer complexation with chloranilic acid

Peer review under responsibility of Taibah University

Figures & data

Fig. 1 Structure of olanzapine.

Table 1 R_f values for reversed phase thin layer chromatographic analysis.

Mobile phase systems	OLP	OLP–CAA Complex	CAA
Acetonitrile:Water (6:4)	0.53	0.49	0.70
Methanol:Water (6:4)	0.16	0.12	0.86

OLP, olanzapine; CAA, chloranilic acid.

Fig. 2 Absorption of spectra of the charge-transfer complexation between olanzapine and chloranilic acid overlaid on chloranilic acid.

Fig. 3 Optimization of temperature for the charge-transfer complexation between OLP and CAA.

Fig. 4 Effect of time of reaction on complex formation at 30 °C.

Fig. 5 Stoichiometric ratio determination for the reaction between CAA and OLP.

Table 2 Analytical and validation parameters for the CT complexes of OLP with CAA.

Parameter	Olanzapine (OLP)
Beer's law limits (μg mL^−1)	2–40
Limit of detection (μg mL^−1)	1.57
Limit of quantitation (μg mL^−1)	4.77
Molar absorptivity (L mol^−1 cm^−1)	(2.302 ± 0.262) × 10^3
Sandell's sensitivity (μg mL^−1 per 0.001 absorbance unit)	0.195
Regression equation^a
Intercept ± 95%CI	0.05793 ± 0.20 × 10^−2
Slope ± 95%CI	0.00514 ± 0.31 × 10^−2
Correlation coefficient, r	0.9977
Formation constant^b, K	6.279 × 10^9

a Y = bX + a, where Y is the absorbance for concentration X μg mL⁻¹.

b Estimated from Benesi-Hildebrand plot.

Table 3 Intra-day and inter-day accuracy and precision of the charge-transfer complexation method.

Assessment	Amount taken (μg mL^−1)	Amount found (μg mL^−1)	Recovery (%)	RSD (%)^c	Relative error (%)
Intra-day^a	5	5.048	100.96	0.83	0.96
	15	15.140	100.94	0.32	0.93
	30	30.267	100.89	0.32	0.89
Inter-day^b	5	5.049	100.98	1.12	0.98
	15	15.124	100.83	0.48	0.83
	30	30.380	101.26	0.41	1.27

a Average of six determinations.

b Average of 12 determination.

c RSD, relative standard deviation.

Fig. 6 Benesi-Hildebrand plot for the charge-transfer complexation.

Table 4 Physicochemical parameters for the formation of CT-complex between olanzapine and chloranilic acid.

Drug	CT λmax (nm)	hνCT (eV)	f	μEN (Debye)	RN (eV)	ID (eV)	W (eV)
MZ	520	2.303	7.289	0.892	4.687	6.054	2.651

Fig. 7 Plot of log K of OLP–CAA complexes as a function of 1/T (K⁻¹).

Table 5 Thermodynamic changes following complexation between olanzapine and chloranilic acid.

Temperature (K)	Molar absorptivity, ɛ (L mol^−1 cm^−1)	Formation constant, K (M^−1)	ΔG° (kJ mol^−1)	ΔH (kJ mol^−1)	ΔS (kJ mol^−1)
303	1.687 × 10^3	1.9014 × 10^10	−59.635		0.1997
323	1.656 × 10^3	1.8661 × 10^10	−63.521	−0.8803	0.1994
333	1.625 × 10^3	1.8310 × 10^10	−65.435		0.1991
353	1.609 × 10^3	1.8133 × 10^10	−69.369		0.1990

ΔG° is the free energy change, ΔH is the enthalpy change and ΔS is the entropy change.

Scheme 1 Formation of charge-transfer complexation between olanzapine and chloranilic acid.

Table 6 Comparative dosage form analysis using the new method and official HPLC method.

Drug formulation	New method^a		HPLC method^a		Mean recovery ± S.D. (%)^b	Error (%)	Statistics (p values)^c
	Amount found (g)	% RSD	Amount found (g)	% RSD			F-ratio test	t test
Lanzep 10^®	20.93	0.46	20.70	1.45	101.10 ± 0.47	1.10	0.05	0.59
Glenmark^®	20.44	2.85	20.60	1.94	99.23 ± 2.83	0.77	0.83	0.77
Olanza 10^®	20.87	0.37	20.71	1.40	100.77 ± 0.38	0.77	0.05	0.68

a Mean value, n = 6. Content of OLP stated by Indian Pharmacopoeia ranges from 90% to 110%.

b % recovery calculated as a ratio of the new method to the official method.

c Statistical analyses done between the results obtained from the proposed method and the official method.