Stability of tramadol with three 5-HT₃ receptor antagonists in polyolefin bags for patient-controlled delivery systems

Figures & data

Table 1 Validation of HPLC method

Compound	Measured concentrations (mg/mL)	Accuracy (%)	Precision, RSD (%)
			Intraday	Interday
Tramadol hydrochloride	0.5	101.2	0.9	1.6
	1.0	99.4	0.4	0.8
	1.5	100.6	0.8	1.1
Ondansetron hydrochloride	0.004	98.8	0.5	1.9
	0.008	99.7	1.0	1.7
	0.012	101.1	0.4	0.8
Granisetron hydrochloride	0.003	98.7	0.8	1.4
	0.006	99.8	0.5	2.1
	0.009	100.2	0.6	0.9
Tropisetron hydrochloride	0.004	100.6	1.1	1.7
	0.005	101.5	0.3	1.2
	0.008	99.2	0.4	0.9

Abbreviations: HPLC, high-pressure liquid chromatography; RSD, relative standard deviation.

Figure 1 Chromatograms of standard drug mixture samples obtained after 20 μL direct injection.

Notes: Retention times were 6.3 minutes for tramadol hydrochloride (peak 1), 7.9 minutes for granisetron hydrochloride (peak 2), 10.7 minutes for ondansetron hydrochloride (peak 3), and 12.5 minutes for tropisetron hydrochloride (peak 4).

Table 2 Stability of tramadol hydrochloride and ondansetron hydrochloride in 0.9% sodium chloride stored in polyolefin bags at 4°C and 25°C

Temperature	Drug	Initial concentration (mg/mL)a	Initial concentration remaininga, mean ± SD (%)
			Day 1	Day 3	Day 5	Day 7	Day 10	Day 14
4°C	Tramadol hydrochloride	10.3±0.46	99.7±0.4	100.8±0.3	100.9±0.4	99.4±0.2	101.8±0.1	101.4±0.2
	Ondansetron hydrochloride	0.083±0.005	100.1±1.5	102.2±1.0	102.1±2.6	100.3±1.3	101.4±1.1	102.3±1.5
25°C	Tramadol hydrochloride	10.3±0.49	99.8±0.4	98.6±0.1	100.2±0.2	99.7±0.3	101.5±0.2	99.8±0.2
	Ondansetron hydrochloride	0.082±0.004	100.9±1.9	100.3±0.4	101.1±1.6	101.6±0.2	97.9±0.3	101.6±0.7

Notes:

a n=3. Data presented as mean ± standard deviation.

Abbreviation: SD, standard deviation.

Table 3 Stability of tramadol hydrochloride and granisetron hydrochloride in 0.9% sodium chloride stored in polyolefin bags at 4°C and 25°C

Temperature	Drug	Initial concentration (mg/mL)a	Initial concentration remaininga, mean ± SD (%)
			Day 1	Day 3	Day 5	Day 7	Day 10	Day 14
4°C	Tramadol hydrochloride	10.7±0.43	100.0±0.2	100.9±0.1	99.4±0.2	99.4±0.3	100.0±0.3	99.9±0.1
	Granisetron hydrochloride	0.062±0.004	100.7±0.5	101.6±0.6	101.5±1.0	100.3±0.9	101.7±2.1	100.5±1.0
25°C	Tramadol hydrochloride	10.3±0.38	99.6±0.1	101.6±0.5	100.7±0.1	101.9±0.2	101.2±0.1	101.5±0.1
	Granisetron hydrochloride	0.063±0.001	100.2±0.6	98.1±1.1	100.7±1.2	101.2±2.2	101.8±1.8	101.7±0.4

Notes:

a n=3. Data presented as mean ± standard deviation.

Abbreviation: SD, standard deviation.

Table 4 Stability of tramadol hydrochloride and tropisetron hydrochloride in 0.9% sodium chloride stored in polyolefin bags at 4°C and 25°C

Temperature	Drug	Initial concentration (mg/mL)a	Initial concentration remaininga, mean ± SD (%)
			Day 1	Day 3	Day 5	Day 7	Day 10	Day 14
4°C	Tramadol hydrochloride	10.2±0.39	100.5±0.5	102.8±2.5	101.4±0.3	101.9±0.5	102.1±0.2	102.3±0.2
	Tropisetron hydrochloride	0.052±0.001	100.2±0.3	100.8±0.8	100.4±0.6	99.8±0.4	100.6±1.0	99.7±0.5
25°C	Tramadol hydrochloride	10.5±0.61	100.9±0.5	99.3±1.0	100.3±0.3	98.4±0.4	101.0±0.8	102.5±0.5
	Tropisetron hydrochloride	0.051±0.003	100.2±0.3	98.6±0.9	102.5±0.4	100.2±0.6	102.1±1.4	101.5±0.8

Notes:

a n=3. Data presented as mean ± standard deviation.

Abbreviation: SD, standard deviation.

Table 5 pH values (mean ± SD [%]; n=3) of tramadol hydrochloride and 5-HT₃ antagonists in polyolefin bags at different storage conditions

Storage period (day)	Tramadol + ondansetron stored at		Tramadol + granisetron stored at		Tramadol + tropisetron stored at
	4°C	25°C	4°C	25°C	4°C	25°C
0	6.25±1.5	6.19±0.2	6.66±0.9	6.68±1.0	5.52±0.2	5.46±0.2
1	6.21±0.6	6.21±0.4	6.62±0.6	6.57±0.7	5.54±0.2	5.49±0.1
3	6.27±0.2	6.24±0.0	6.68±0.2	6.55±0.1	5.55±0.3	5.46±0.1
5	6.25±0.1	6.21±0.8	6.75±0.2	6.72±0.3	5.59±0.0	5.52±0.8
7	6.25±1.3	6.25±0.2	6.68±0.8	6.63±1.2	5.54±0.4	5.41±0.6
10	6.27±0.1	6.26±0.1	6.72±0.1	6.66±0.5	5.62±0.1	5.55±0.3
14	6.22±0.1	6.23±2.1	6.70±0.9	6.70±0.6	5.58±0.2	5.51±0.1

Abbreviations: 5-HT₃, 5-hydroxytryptamine-3; SD, standard deviation.