Food Chemistry 127 (2011) 5462

Contents lists available at ScienceDirect

Food Chemistry
journal homepage: www.elsevier.com/locate/foodchem

Inorganic elemental compositions of commercial multivitamin/mineral dietary

supplements: Application of collision/reaction cell inductively
coupled-mass spectroscopy
Bharathi Avula a, Yan-Hong Wang a, Nurdan S. Duzgoren-Aydin a,1, Ikhlas A. Khan a,b,
a
b

National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, MS 38677, USA
Department of Pharmacognosy, School of Pharmacy, The University of Mississippi, MS 38677, USA

a r t i c l e

i n f o

Article history:
Received 29 September 2010
Accepted 17 December 2010
Available online 24 December 2010
Keywords:
ICP-MS
Multivitamin/mineral dietary supplements
Microwave digestion
Inorganic elements

a b s t r a c t
Thirty ve different commercially available multivitamin/mineral (MVM) dietary supplements in tablet,
capsule, liquid or powder form for children, women, men, young and adult consumption were analysed
by collision/reaction cell ICP-MS for their inorganic elemental compositions including Na, Mg, K, Ca, V, Cr,
Mn, Fe, Ni, Cu, Zn, As, Se, Cd, Hg, and Pb. Samples were digested with concentrated nitric and hydrochloric
acid (8:2) using a closed vessel microwave system. The validity of the applied method was assessed by
the analysis of standard reference materials (SRM 3280, SRM 1566b) and of spiked samples. Special
emphasis was given to the percentage deviation of calculated daily intake of each analysed element from
their corresponding label claim. Additionally, for toxic elements calculated daily intake values are compared with those of the regulatory guideline values (e.g., recommended dietary allowance). The results
revealed that all analysed products have calculated daily intake of As, Cd, Pb and Hg concentrations lower
than those of the regulatory limits. The percentage differences between the calculated and claimed daily
intake values varied moderately (20%) to signicantly (>30%) for the potentially toxic elements, especially
Cr, Se, Mn, and Zn. Furthermore, it is not uncommon for the same product to have high, as well as low,
elemental compositions compared to their corresponding claimed values.
2010 Elsevier Ltd. All rights reserved.

1. Introduction
The demand for multivitamin/mineral dietary supplements has
been increased signicantly in the last couple of decades, especially in the industrialised countries including the US, Canada
and North Europe (Eisenberg et al., 1998). In the USA, commercially available vitamins and dietary supplements are regulated
under the Dietary Supplement Health and Education Act of 1994
(DSHEA) by the US Food and Drug Administration (FDA). Recently
published FDA regulations hold supplement manufacturers or distributors responsible for the content of the dietary supplement
which should only contain what they are labelled and not any
harmful or undesirable substances, including pesticides and heavy
metals (Mindak, Cheng, Canas, & Bolger, 2008).
There has been an increasing number of studies focusing on elemental compositions of multivitamin/dietary supplements in order
to assess their safety for public consumption (Dolan, Nortrup,
Bolger, & Capar, 2003; Mindak et al., 2008; Raman, Patino, & Nair,
Corresponding author at: Department of Pharmacognosy, School of Pharmacy,
The University of Mississippi, MS 38677, USA.
E-mail address: ikhan@olemiss.edu (I.A. Khan).
1
Current address: Department of Geoscience and Geography, New Jersey City
University, NJ 07305, USA.
0308-8146/$ - see front matter 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.foodchem.2010.12.083

2004). The safety of the multivitamin/dietary supplements

depends on various factors including, but not limited to, growing
conditions of the raw material and its extraction, formulation,
and manufacturing processes (Raman et al., 2004). Several studies
documented that these supplementary materials may contain high
levels of certain elements, especially Pb and As (Amster, Tiwary, &
Schenker, 2007; Mindak et al., 2008) compared to their safe/tolerable exposure levels (provisional total tolerable intake level, PTTI)
(Amster et al., 2007; Mindak et al., 2008). Therefore, determining
elemental compositions of multivitamin/dietary supplements is
crucial.
Most of the previous studies focused on a limited number of
heavy metals/metalloids (Pb, As, Cd, and Hg). It has been, however,
well-established that other elements, particularly Cr, Cu, Zn, and
Mn, which are considered essential elements, may also be toxic
depending on dose. Commercial multivitamin and/or mineral
(MVM) dietary supplements contain a variable type, number and
amounts of essential and non-essential elements. Micronutrients
that should be included in a complete MVM supplements are vitamins A, B-complex, C, D, and E, and the elements Na, Mg, K, Ca, V,
Cr, Mn, Ni, Cu, Zn, Se, and possibly Fe. Although organic components often form the majority of a supplement, metals may be
found due to their inclusion in vitamin structures, such as Co pres-

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B. Avula et al. / Food Chemistry 127 (2011) 5462

ent in vitamin B-12. They may also be added as a contaminant

through natural products or during the manufacturing process.
The aims of this study are to document labelled and non-labelled inorganic elemental compositions of the MVM products
and to determine percentage deviation of the calculated daily intake values with those of the claimed ones, and/or with those of
the regulatory guideline limits such as the minimum risk levels
(MRL), no-observed-adverse-effect levels (NOAEL), tolerable upper
intake levels (UL) or the recommended dietary allowance (RDA). In
this study, 35 different MVM products in tablets, capsules, powders
or liquid forms for children, women, men, young or adult consumption were selected based on their availability in the US market, and were purchased online. Their elemental compositions (Na,
Mg, Al, K, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Cd, Cs, Ba, Tl,
Hg, Pb and U) were determined by using Collision Reaction Cell
(CRC) ICP-MS.

Ni, Cu, Zn, As, Rb, Sr, Cs, Ba, and no gas-mode for Cd, Tl, Hg, Pb and U to
remove spectral interferences. The Integrated Sample Introduction
System (ISIS) was used with a pump speed set at 0.1 rps during the
analysis and washout in order to minimise the amount of matrix
onto the interface and optimise sample throughput.
2.2. Standards and chemicals
Multielement (10 lg/ml), internal standard (10 lg/ml), mercury (10 lg/ml) standard stock solution, tuning mix and PA tuning
solution were purchased from Agilent Technologies (Agilent Technologies, Palo Alto, CA, USA). Optima grade concentrated nitric and
hydrochloric acid were purchased from Fisher Scientic (Fair Lawn,
NJ, USA). Water was puried in a Milli-Q system (Millipore, Bedford, MA, USA).
2.3. Calibration standards

2. Materials and methods

2.1. Instrumentation
The Agilent 7500ce octopole reaction system ICP-MS (Model
#G3272A, Agilent Technologies, Palo Alto, CA, USA) was used in
the study. Internal standard (Ge) was introduced via the micromist
nebulizer to the spray chamber via the peristaltic pump of the ICPMS. The pulse to analogue factor (P/A) was determined on each
day of analysis and the tuning of the instrument was carried out
using an Agilent ICP-MS tuning solution (10 lg/l, Ce, Co, Li, Y and
Tl solution). The system was aspirated with 3% nitric acid for
30 min before performing the tuning of the instrument. The instrument operating conditions are illustrated in Table 1. The total analysis time was 6 min in multi-tune mode followed by a 2-min rinse in
2% nitric acid. The instrument is operated in hydrogen mode (H2) for
Se, Ca and Fe, and helium (He) mode for Na, Mg, Al, K, V, Cr, Mn, Co,

The concentrations of the standards ranged from 0.1 to 100 ng/

ml for Hg, from 100 to 5000 ng/mL for K and from 1 to 5000 ng/ml
for Na, Mg, Al, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Cd, Cs,
Ba, Tl, Pb and U to ensure that unknown samples were within the
range of the standards. Seven-point external calibrations with
standards were used to quantify the elements in the digests. Germanium (Ge) as an internal standard, added on-line (50 ng/mL).
2.4. Samples and reference materials
Multivitamin/mineral (MVM-1 to MVM-35) products were purchased online in the year 2009. Of the 35 products purchased, 15
supplements contained herbs or botanicals as other ingredients.
The MVM products purchased revealed a variety of products
described as multivitamin, multimineral, multiple nutrients, ultraminerals and multivitamin/mineral. These also include specialised

Table 1
Operating conditions for the ICP-MS equipped with an octapole reaction system.
ICP Conditions
Plasma power (W)
Reected power (W)
Carrier gas (l/min)
Make up gas (l/min)
Aux. gas (l/min)
Plasma gas (l/min)
Sample up-take
Nebulizer
Sample tube (mm, id)
Internal standard tube (mm, id)
Waste tube (mm, id)
Spray chamber
Interface cones
Octopole reaction system
Cell gas
Cell gas ow rate (ml/min)
Cell entrance (V)
QP focus (V)
Cell exit (V)
OctP bias (V)
QP bias (V)
Extract 1 (V)
Extract 2 (V)
Omega Bias (V)
Oct P RC (V)
Points/peak
Repetitions
Integration time /mass (sec)
Acquisition mode
Total analysis time (multi-tune)
Rinse time

1500
12
0.9
0.15
0.9
15
400 ll/min
Glass concentric, micromist
1.02
0.19
1.52
Quartz cooled to 2 C
Ni
Standard mode (no gas), H2 and He modes
No Gas
0
30
3
30
6
3
0
110
28
150
3
3
0.3
Multi-tune and scanning
6 min
3 min

He
3.9
30
10
40
18
14
0
110
26
150

H2
5.0
30
8
40
18
16
0
110
26
150

56

B. Avula et al. / Food Chemistry 127 (2011) 5462

products, namely MVMs for men, women, adults aged 50+, children, persons with diabetes, cardio, performance, energy, seniors
and young. Nine products (MVM-3, MVM-7, MVM-12, MVM-14,
MVM-15, MVM-23, MVM-26, MVM-28 and MVM-35) do not
include MVM terms in their names, but contain similar types and
amounts of vitamins and minerals as MVM labelled products.
The 35 MVM products varied in the types, amounts of vitamins/
minerals they contained and a few others contained other nonvitamin and non-mineral ingredients (e.g., dietary bre, botanicals,
glucosamine, lycophene, rice protein concentrate, spirulina, fruit
extract, bioavonoids, and phytosterols). Two products (MVM-22,
33) bearing the same brand name are in different forms (e.g., solid
and liquid), but differ in composition.
The extraction method was validated using the reference materials from the National Institute of Standards and Technology
(NIST; Gaithersburg, MD, USA), namely multivitamin/multielement tablet (SRM 3280) and oyster tissue (SRM 1566b).
2.5. Experimental
2.5.1. Sample preparation
The dietary supplements analysed in this work were in multiple
dosage forms including tablets, capsules, powders and liquids. In
order to perform the determinations on these different matrices
we developed an extraction protocol specic for each class of
formulation.
2.5.2. For tablets/capsules
For tablets, 20 tablets were weighed and then pulverised with a
mortar and pestle. For capsules, 20 capsules were weighed; the
contents were emptied, then mixed and triturated in a mortar
and pestle. All ground samples were passed through a # 40 sieve
(with particles smaller than 0.420 mm).
About 0.2 g of powdered tablet or capsule contents were
weighed into microwave digestion vessels and 10.0 ml of concentrated nitric and hydrochloric acid (8:2) mixture was added. The
samples were digested and assayed under optimised conditions.
2.5.3. For liquids
2.0 ml solution was added into microwave digestion vessel and
8 ml of concentrated nitric and hydrochloric acids (8:2) mixture
was added. The samples were digested and assayed under optimised conditions.
2.5.4. Microwave digestion
The digestion of samples was conducted as described by Avula,
Wang, Smillie, Duzgoren-Aydin, and Khan (2010). The digestion
programme consisted of a brief ramp time of 5 min to reach
180 C and a digestion was performed for 15 min at a power of
1600 W. The vessels were cooled and opened. Digestion was
judged to be complete when the temperature reached 180 C and
light yellow, clear solutions were produced. The samples were
cooled, ltered and 1.0 ml of ltrate was then diluted to 10 ml with
water. Blanks (10 ml of solvents) were digested in the same manner. The amounts of acids used were the same as the amounts of
additives to the digested samples in the digestion batch. Final solutions for determination of Na, Mg, Al, K, Ca and Fe were further diluted two-fold up to ten-fold.
2.5.5. Validation procedure
The developed ICP-MS method was validated in terms of precision, accuracy, and linearity according to ICH guidelines (ICH,
1996). The limit of detection (LOD) and limit of quantication
(LOQ) were determined by injecting a series of dilute solutions with
known concentrations. Intra- and inter-day variation of the assay
was determined on three consecutive days with three repetitions

each. Standard solutions were also analysed after every seven samples to ensure instrument performance. The contamination of the
digestion procedure and sample manipulation was overcome by
the use of a blank solution containing no samples and was analysed
together with the samples.
3. Results and discussion
3.1. Accuracy, precision and linearity
Seven point calibration curves for all 24 elements showed a linear correlation (Table 2). Calibration data indicated the linearity
(r2 > 0.999) of the detector response 0.1100 ng/ml for Hg, from
100 to 5000 ng/ml for K and from 1 to 5000 ng/ml for Na, Mg, Al,
Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Cd, Cs, Ba, Tl, Pb
and U. All standards and samples were injected in triplicate. Multiple injections showed that the results are highly reproducible and
showed low standard error. Accuracy of the method was conrmed
by performing a recovery experiment. Intra- and inter-day variation of the assay was determined and RSD was found to be lower
than 6.0%. Compared to the theoretical amounts, recoveries of
96103%, except for Al which was about 92%, were obtained (Table
3). An indicator of the precision of a method was the standard deviation. All samples analysed in this study were injected in triplicate
and the calculated standard deviation was below 6.0% for all elements. The intraday RSD for the SRMs (n = 9) ranged from 0.38%
to 5.76% for all elements while that for the samples (n = 6) ranged
from 0.55% to 3.79%. The day to day RSD for the SRMs (n = 3) ranged from 0.31% to 4.66%, while that for the samples (n = 3) ranged
from 0.46% to 4.19%.
3.2. Interferences and memory effects
The CRC ICP-MS was equipped with a highly efcient octapole
reaction system, allowing careful control of ion energy. Most
polyatomic and a few argon based interferences of 40Ar16O on
56Fe, 39K16O on 55Mn, 44Ca16O on 60Ni, 40Ar23Na on 63Cu,
interferences from the chlorine matrix or undigested organo-carbon matrices were removed using He collision mode, while the

Table 2
Calibration data [regression equation and correlation coefcient (r2)], detection limits
(DL) and background equivalent concentration (BEC) for elements.
Element

Mass

Mode

r2

DL(ng/ml)

BEC (ng/ml)

Na
Mg
Al
K
Ca
V
Cr
Mn
Fe
Co
Ni
Cu
Zn
As
Se
Rb
Sr
Cd
Cs
Ba
Tl
Hg
Pb
U

23
24
27
39
40
51
52
55
56
59
60
63
66
75
78
85
88
111
133
137
205
201
208
238

He
He
He
He
H2
He
He
He
H2
He
He
He
He
He
H2
He
He
No
He
He
He
No
No
No

1.0000
0.9999
1.0000
0.9998
0.9999
1.0000
0.9999
0.9999
1.0000
0.9999
0.9998
0.9999
0.9998
0.9999
1.0000
0.9999
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000

0.84
0.96
0.93
40.23
1.11
0.05
0.007
0.15
0.36
0.12
0.074
0.07
0.70
0.055
0.17
0.10
0.06
0.19
0.04
0.038
0.04
0.011
0.015
0.18

20.87
10.85
15.78
67.45
17.12
0.065
0.63
1.1
4.2
0.58
0.76
1.22
3.83
0.64
0.27
0.58
0.59
0.44
0.54
0.087
0.52
0.027
0.078
0.31

gas

gas
gas
gas

57

B. Avula et al. / Food Chemistry 127 (2011) 5462

Table 3
Measured and certied values for two certied reference materials. All certied elements are reported for each reference material, not all materials are certied for all elements.
Element

NIST SRM 3280

Certied value (mg/g)
0.33 0.020a
67.8 4.0

Na
Mg
Al
K
Ca
V
Cr
Mn
Fe
Co
Ni
Cu
Zn
As
Se
Rb
Sr
Cd
Ba
Hg
Pb
U
a

NIST SRM 1566b

Measured value (mg/g)

Certied value (mg/g)

Measured value (mg/g)

0.337 0.019
65.17 3.04
197.2 6.0

53.1 7.0
110.7 5.3
0.008 0.002
0.094 0.0027
1.44 0.11
12.35 0.91
0.00081 0.01
0.0084 0.0008
1.4 0.17
10.15 0.81

51.95 1.17
106.31 0.553
0.0082 0.0003
0.091 0.005
1.392 0.047
11.97 0.553
0.00082 0.0001
0.00839 0.0004
1.335 0.063
9.903 0.160

0.0176 0.0008

0.0170 0.0004

0.0298 0.2

0.0296 0.002

181.067 1.266

7.65 0.65

7.717 0.031

3.26 0.145
6.8 0.2
2.48 0.08
8.6 0.3
0.037 0.0013
0.308 0.009
0.2550 0.0014

3.37 0.036
6.93 0.058
2.466 0.005
8.747 0.095
0.0381 0.001
0.3113 0.002
0.260 0.001

Mean values SD.

Table 4
Recommended dietary allowances/minimum risk levels/no-observed-adverse-effect levels of the elements/day.
Elements

RDA/MRL/NOAEL/UL/AI

Reference

Na
Mg
Al

[Institute of Medicine. Food and Nutrition Board, 2004]

[Institute of Medicine. Food and Nutrition Board, 1999]
[Agency for Toxic Substances and Disease Registry (ATSDR), 2008]

K
Ca
V

AI 1.5 g for adults

RDA 420 mg for men and 320 mg for women
DI 0.100.12 mg Al/kg/day for adults NOAEL 26 mg Al/kg/
day
AI 4.7 g for adults
AI 1000 mg for adults
MRL 210 lg

Cr
Mn
Fe
Co
Ni
Cu
Zn
As

RDA 35 lg for males and 25 lg for females

RDA 2.3 mg for men and 1.8 mg for women UL-11 mg
RDA 8 mg for men and 18 mg for women
0.0051.8 mg daily dietary intake
UL 1 mg
RDA 900 lg for adults, NOAEL 10 mg
AI 11 mg for men and 8 mg for women
MRL 21 lg; 10 lg for adults (ANSI 173)

Se
Rb
Sr

RDA 55 lg for adults-RDA, UL 400 lg for adults

15 mg
MRL 2.0 mg/kg/day. Total estimated daily exposure: 3.3 mg
(0.046 mg/kg/day)
MRL 14 lg
0.0040.03 mg Daily dietary intake
0.61.7 mg Daily dietary intake
0.0015 mg Daily dietary intake
50 lg for adults; 20 lg for adults (ANSI 173)
75 lg for adults, 6 lg for children; 20 lg for adults (ANSI
173)
MRL 140 lg

Cd
Cs
Ba
Th
Hg
Pb
U

[Institute of medicine, 2004]

[Institute of medicine, 1999; Institute of Medicine. Otten, Pitzi Hellwig, and Meyers, 2006]
[Dietary Reference Intakes for Vitamin A et al., 2000; Agency for Toxic Substances and
disease Registry (ATSDR), 2009]
[Institute of medicine, 2006; Dietary Reference Intakes, 2000]
[Institute of medicine, 2006; Dietary Reference Intakes, 2000]
[Institute of medicine, 2004; Institute of medicine, 1999]
[Dietary Reference Intakes, 2000]
[Dietary Reference Intakes, 2000]
[Institute of medicine, 2006], [Dietary Reference Intakes, 2000]
[Institute of medicine, 2006; Dietary Reference Intakes, 2000]
[Institute of medicine, 2006; Agency for Toxic Substances and disease Registry (ATSDR),
2007a]
[Institute of Medicine. Food and Nutrition Board, 2000]
[Nielsen (1996)]
[Agency for Toxic Substances and Disease Registry (ATSDR), 2004a]
[Agency for Toxic Substances
[Agency for Toxic Substances
[Agency for Toxic Substances
[Agency for Toxic Substances
[Dolan et al., 2003]
[Carrington & Bolger, 1992]

and
and
and
and

disease Registry (ATSDR), 2007b]

Disease Registry (ATSDR), 2004b]
disease Registry (ATSDR), 2007c]
Disease Registry (ATSDR), 1995]

[Agency for Toxic Substances and disease Registry (ATSDR), 1999]

Adequate intakes (AI), daily intakes (DI), tolerable upper intake levels (UL), recommended dietary allowances (RDA), minimum risk levels (MRL), no-observed-adverse-effect
levels (NOAEL).

few argon based polyatomics were efciently removed using H2

in reaction mode in complex and variable matrices. Elemental
measurements were performed using CRC ICP-MS operating in
hydrogen-mode for Se, Ca and Fe, helium-mode for Na, Mg, Al,
K, V, Cr, Mn, Co, Ni, Cu, Zn, As, Rb, Sr, Cs, Ba and no gas-mode
for Cd, Tl, Hg, Pb and U to remove spectral interferences and all

the data acquired using a single method with no correction equations required.
One problem that does occur is the long memory effect between
samples caused by the contact of mercury with the materials that
comprise the sample introduction system. This was usually overcome by extended washing periods between samples, using the

58

B. Avula et al. / Food Chemistry 127 (2011) 5462

Table 5
Label claim (mg/serving size) of elements in various multivitamin/mineral dietary supplements.
Samples

Claim, mg/serving size

Na

MVM-1
MVM-2
MVM-3
MVM-4
MVM-5
MVM-6
MVM-7
MVM-8
MVM-9
MVM-10
MVM-11
MVM-12
MVM-13
MVM-14
MVM-15
MVM-16
MVM-17
MVM-18
MVM-19
MVM-20
MVM-21
MVM-22
MVM-23
MVM-24
MVM-25
MVM-26
MVM-27
MVM-28
MVM-29
MVM-30
MVM-31
MVM-32
MVM-33
MVM-34
MVM-35

60

10
10

15

2
7

30

Mg

Ca

40
84
60
100
100
50
7.7
40
500
20
50
20
100
100
50
40
40
250
100
250
100
125

10
17
200

125
166
50
500
40
220
50
100
1000
100
220
100
150
200
450
250
108
500
200
400
200
250
10
150
1113
120
100
5
1125
25
50
40
100
50
600

75
200
100
50
1
200
10
50
20
40
50
50

7.5
80
10
80
99
80
25
80
99
64
50

50
1
40
40
25
7
99
25
10
50
45

Cr

Mn

0.01
0.01
0.01

0.04
0.066
0.01
0.12
0.05
0.045
0.01
0.12
0.1

2
1.7
0.5
2
2
2.3
6.1
4
10

0.045

2.3

0.01

Fe

9
10
18
5
18

Ni

0.005
0.005
0.005

0.005
18

0.005
0.01
0.01
0.010
0.01
0.08

0.01

dilute solutions of Hg for calibration curve and the use of hydrochloric acid as well as nitric acid in the matrix.

0.02
0.5
0.12
0.1
0.120
0.2
0.035
0.2
0.2
0.12
0.06
0.06
0.05
0.18
0.15
0.001
0.05
0.01
0.12
0.1
0.12
0.12

2
2
2
2
2
2
2.3
15
2
4
1
2
4
4
5
4
2
10
6
4
3
1.8

0.005
18
9
6

0.005
0.005

18

0.005

6
0.8
3
9

10
0.1

Cu

Zn

Se

0.2
0.3

2
5
15
15
15
11
15
11
15
12
11
12
2.5
15
15
15
7.5
15
11
30
10
15
8
15
15
22.5
15
0.17
15
3
15
15
15
15
7.5

0.02
0.066
0.017
0.07
0.07
0.055
0.025
0.07
0.1

2
2
0.9
0.25
0.9
1
2
0.9
2
0.25
2
2
2
0.7
1.5
0.9
1.5
1
2
1.5
1
0.2
2
2
0.2

11
1
9

2
1
2
1
1

0.055
0.02
0.07
0.02
0.045
0.02
0.2
0.055
0.1
0.2
0.07
0.05
0.035
0.05
0.105
0.05
0.0007
0.05
0.015
0.2
0.05
0.07
0.105

mended dietary allowance (RDA) for each element. The MRLs,

ULs, RDAs and NOAELs of the metals analysed in the supplements are shown in Table 4.

3.3. Method performance

3.4. Analysis of dietary supplements
The results of replicate analyses of reference materials (0.1
0.3 g) were used to assess accuracy and precision. Methodology
developed on the ICP-MS was tested through analysis of NIST
reference materials (SRM 3280, multivitamin/multielement tablet; SRM 1566b, oyster tissue). The samples were measured
and carried through the same digestion procedure, along with
the supplement materials. Table 3 shows the results obtained
for SRM 3280 and SRM 1566b which is mostly in agreement
with the certied values (within 10%). The standard reference
materials were used in validating analytical methods for the
determination of vitamins and elements in dietary supplement
formulations. The results from duplicate sample preparations
are in good agreement with each other. Generally less than
20% relative percent difference is acceptable and these range
from 1% to 11%. The blank solutions spiked with multielement
and Hg standards prior to microwave digestion, the resultant
recoveries fell within 100 10% (n = 6) of the expected values.
A post-digestion spike on these supplements (1 ng/ml for As,
Cd, Cr, Pb, Hg, Se, and 100 ng/ml for other elements) showed
good recoveries, further supporting that both method and instrument were operating as expected. The concentration of metals
present in the supplements studied were compared with the
minimum risk levels (MRL), the no-observed-adverse-effect levels (NOAEL), tolerable upper intake levels (UL) or the recom-

ICP-MS has clear advantages in its multi-element characteristics, speed of analysis, and detection limits. Octopole ICP-MS has
been used for separation of analyte signals from known spectral
interferences. Sample digestion using a microwave procedure and
analysis were based on a method developed for multi-element
analysis of botanicals using ICP-MS (Avula et al., 2010). A total of
24 elements have been determined in 35 of the most commonly
used MVM dietary supplements, either in capsule, tablet, liquid
or powder form, in the USA. As indicated above, special emphasis
was given to the percentage difference between the calculated
daily intake value of the each analysed element and those of the
corresponding claimed values. All products analysed were combination products containing a variety of different ingredients. There
is no standard protocol or content uniformity requirements
specied for multivitamin/mineral. The USP 32-NF 27 General
Chapter < 905 > Uniformity of Dosage Units lists standard test
methods for the quality of oral dosage forms. They are divided into
different categories: performance test for oral drug products (Pharmaceuticals) and performance test for dietary supplements. The
characterisation and quality control of pharmaceutical dosage
forms is much more closely controlled compared to dietary supplements. The uniformity of dosage units can also be demonstrated by
either of two methods, weight variation or content uniformity. The

59

B. Avula et al. / Food Chemistry 127 (2011) 5462

Table 6
Content (mg/serving size) of elements in various multivitamin/mineral dietary supplements (n = 3).
Samples

MVM-1
MVM-2
MVM-3
MVM-4
MVM-5
MVM-6
MVM-7
MVM-8
MVM-9
MVM-10
MVM-11
MVM-12
MVM-13
MVM-14
MVM-15
MVM-16
MVM-17
MVM-18
MVM-19
MVM-20
MVM-21
MVM-22
MVM-23
MVM-24
MVM-25
MVM-26
MVM-27
MVM-28
MVM-29
MVM-30
MVM-31
MVM-32
MVM-33
MVM-34
MVM-35

Mg/serving size
Na

Mg

Al

Ca

Cr

Mn

Fe

Co

Ni

Cu

0.725
3.07
42
1.09
1.74
1.84
0.444
0.380
16.3
5.91
0.608
7.78
1.01
2.45
1.58
1.67
6.14
4.35
2.61
4.01
1.63
16.4
3.65
2.34
4.59
2.779
2.02
1.65
6.66
1.03
7.80
3.87
21.2
5.61
1.04

38.1
62.1
41.7
80
90.3
43.9
6.13
34.2
399
16.4
39.3
18.8
79.5
81.9
39.5
32.8
35.3
160
73.01
224
79.5
66.3
2.57
63.8
160
80.3
47.4
1.88
1187
10.4
42.9
17.1
44.9
39.9
46

0.07
0.086
0.102
0.335
1.13
0.336
0.146
0.921
1.26
2.41
0.274
1.97
0.085
0.198
0.288
0.381
0.349
0.315
0.122
0.156
0.141
0.206
0.044
0.024
0.729
0.185
0.076
0.058
0.871
0.056
0.114
0.040
0.399
0.051
0.572

6.96
11.9
176
0.555
6.57
72.5
9.82
72.9
87.8
0.184
64.3
1.41
18
64.2
0.415
85.8
62.1
59.9
64.7
6.60
1.99
35.6
16.4
30.1
133
32.2
23.1
10.9
160
29.5
21.84
9.10
86.5
38.8
0.435

110
237
34.8
503
52.2
216
60.1
104
1.01x103
117
218
102
162
364
434
252
118
400
192
464
193
146
15.6
280
1.02x103
146
120
19.6
1.02x103
30.1
71
37.7
120
85.4
633

0.008
0.002
0.012
0.016
0.012
0.013
0.002
0.010
0.049
0.002
0.010
0.001
0.009
0.011
0.003
0.012
0.018
0.007
0.012
0.070
0.002
0.009
0.001
0.012
0.023
0.002
0.004
0.001
0.021
0.002
0.002
0.002
0.007
0.004
0.003

0.036
0.040
0.012
0.096
0.058
0.045
0.015
0.116
0.186
0.004
0.045
0.004
0.017
0.438
0.155
0.119
0.248
0.138
0.031
0.161
0.177
0.076
0.060
0.056
0.060
0.179
0.136
0.003
0.059
0.011
0.101
0.113
0.134
0.116
0.004

1.67
1.76
0.425
1.62
1.82
2.23
5.16
3.57
8.06
0.036
1.81
0.077
1.75
1.66
1.71
1.71
1.92
1.25
1.85
11.9
1.60
2.02
0.916
1.64
3.51
3.39
4.26
0.030
3.91
1.88
8.71
5.79
3.9
2.53
1.64

0.078
0.175
0.113
0.618
7.61
0.230
11
16.5
5.82
14.3
0.137
17.5
0.134
0.335
15.8
8.14
6.62
0.478
13.0
0.314
5.20
0.456
3.34
7.71
1.27
0.055
7.99
0.172
1.27
0.076
0.216
10.4
0.704
8.52
0.251

0.002
0.002
0.002
0.002
0.001
0.003
0.003
0.002
0.019
0.001
0.001
0.001
0.002
0.002
0.002
0.002
0.011
0.007
0.001
0.034
0.002
0.005
0.001
0.002
0.005
0.002
0.003
0.002
0.009
0.005
0.005
0.005
0.012
0.007
0.001

0.005
0.004
0.004
0.007
0.007
0.009
0.004
0.012
0.045
0.002
0.012
0.003
0.003
0.012
0.007
0.017
0.016
0.008
0.006
0.009
0.004
0.007
0.004
0.004
0.028
0.004
0.003
0.002
0.016
0.001
0.007
0.002
0.009
0.002
0.005

0.149
0.172
0.004
1.628
1.589
0.769
0.301
0.787
0.890
1.414
0.717
1.70
0.179
1.64
1.57
1.65
0.888
1.10
0.724
1.22
0.914
1.02
1.91
0.944
0.236
1.50
1.64
0.003
0.258
0.001
1.80
0.885
1.981
0.979
0.848

content and the weight of 20 units in a lot were determined for

each product and the acceptance values were calculated according
to the United States Pharmacopeia (2009). In this study, we have
also adapted recent European Pharmacopeia regulations (European
Pharmacopoeia, 5th edition, Supplement 5.2, Council of Europe,
Strasbourg, 2005, Chapter 2.9.40) (Balazs, Banfai, Katalin Ganzler,
eny, 2007) to determine whether the measured data
& Sandor Kem
is in agreement with the label claim. Based on this regulation, if the
% deviation falls within 85% and 115%, the results were accepted as
the measured data is in close agreement with label claim.
Analysis of the present study for samples containing Na, Mg, K,
Ca, V, Cr, Mn, Fe, Cu, Zn and Se in the 35 products ranged from 59%
to 109%, 53% to 188%, 69% to 173%, 58% to 187%, 87% to 179%, 64%
to 285%, 51% to 103%, 57% to 172%, 51% to 129%, 43% to 101% and
53% to 204%, respectively, of label claims (Table 5) except for two
products (MVM-18, 31), which contained 3.9 and 16.4 times more
Ca and K, respectively than the stated value. The results for the
MVM dietary supplements are shown in Tables 5 and 6 and represent the mean of three replicate analyses. Recommended intakes
were expressed as number of capsules or tablets/day (for solid dosage form), and ml/day (for liquids). Estimated maximum daily
intake (mg/day) = to the concentration of element (mg) multiplied
by dilution factor and multiplied by the suggested maximum daily
intake. All of the information about the elements that is listed on
the label is given according to the serving size and suggested use
was one serving size daily for all the products. MVMs vary in types,
amounts of elements they contain and whether they contain other
non-vitamin and non-elemental ingredients (e.g., dietary bre,
botanicals, rice protein and ban). Thirty ve MVM supplements
contained ve to eleven elements. The variability in the vitamin

and elemental contents in food and dietary supplements was considerable, and can exceed 1020% or even more (Feifer, Fleshner, &
Klotz, 2002; Whittakar, Tufaro, & Radar, 2001; Yetley, 2007; Veatch, Brockman, Spate, Robertson, & Morris, 1998). The analytical
data obtained compared with label claim and used for quality control purpose.

3.4.1. Major elements (Na, Mg, K, Ca)

Seven of the 35 products containing Na, thirty four of the 35
products for Mg, twenty ve of the 35 products for K and all thirty
ve products for Ca provided the label claim (Table 5). The content
of Na, Mg, K and Ca were within 100 15% except for products
MVM-3, 10, 12, 28, 33, Na was found to be about 70%, 59%, 78%,
59%, 83%, 71%, respectively; for products MVM-4, 7, 9, 10, 11, 13,
14, 15, 16, 21, 25, 26, 25, 34, Mg content was in the range from
80% to 85% and for MVM-2, 3, 18, 19, 22, Mg content was in the
range from 53% to 74% of label values. For MVM-1, 2, 13, 22, 24,
28, 33, K content was about 70%, 69%, 72%, 71%, 75%, 156% and
173%, respectively. For sample MVM-23, 16.44 mg/serving (claim,
1 mg/serving) K was present. For MVM-22, Ca content was about
58%, for other samples MVM-2, 5, 14, 23, 24, 31, 34; Ca content
was about 1.31.9 times more than the label value, whereas for
sample MVM-28, it was 3.9 times more than the label claim. The
Na/K ratio in samples MVM-4, 10, 12, 35 (between 2 and 32) were
found to be high (Table 6) and favourably low Na/K quotient for all
remaining samples (range 0.0050.61) (Dawczynski, Schafer, Leiterer, & Jahreis, 2007; Institute of Medicine, 2004; Townsend, Fulgoni, Stern, Adu-Afarwuah, & McCarron, 2005; Tsuji, Nakagawa, &
Ichikawa, 1993).

60

B. Avula et al. / Food Chemistry 127 (2011) 5462

Table 7
Content (mg/serving size) of elements in various multivitamin/mineral dietary supplements (n = 3).
Samples

MVM-1
MVM-2
MVM-3
MVM-4
MVM-5
MVM-6
MVM-7
MVM-8
MVM-9
MVM-10
MVM-11
MVM-12
MVM-13
MVM-14
MVM-15
MVM-16
MVM-17
MVM-18
MVM-19
MVM-20
MVM-21
MVM-22
MVM-23
MVM-24
MVM-25
MVM-26
MVM-27
MVM-28
MVM-29
MVM-30
MVM-31
MVM-32
MVM-33
MVM-34
MVM-35

Mg/serving size
Zn

As

Se

Rb

Sr

Cd

Cs

Ba

Tl

Hg

Pb

1.86
3.64
10.3
11.9
11.5
9.10
12.1
9.05
12.4
8.52
8.24
10.1
1.86
11.9
10.7
11.4
6.77
9.48
7.65
24.1
7.96
6.44
7.19
11.1
12.1
22.8
12.1
0.137
11.5
2.86
12.4
13.3
15.2
12
6.47

0.002
0.001
0.005
0.002
0.001
0.001
0.001
0.001
0.008
0.001
0.001
0.001
0.001
0.001
0.002
0.001
0.001
0.003
0.001
0.004
0.001
0.016
0.001
0.001
0.012
0.001
0.001
0.001
0.011
0.002
0.002
0.001
0.008
0.001
0.002

0.014
0.035
0.026
0.061
0.069
0.057
0.021
0.072
0.081
0.0003
0.052
0.0005
0.022
0.057
0.024
0.051
0.041
0.144
0.038
0.089
0.208
0.052
0.051
0.031
0.060
0.084
0.054
0.001
0.062
0.001
0.199
0.057
0.082
0.0997
0.001

0.0015
0.0020
0.0150
0.0012
0.0006
0.0042
0.0011
0.0042
0.0072
0.0004
0.0024
0.0011
0.0015
0.0064
0.0009
0.0062
0.0026
0.0178
0.0029
0.0072
0.0015
0.0062
0.0069
0.0018
0.1000
0.0016
0.0024
0.0060
0.1701
0.0044
0.0142
0.0014
0.0151
0.0024
0.0009

0.050
0.301
0.019
0.181
0.015
0.063
0.017
0.022
0.338
0.026
0.064
0.042
0.079
0.074
0.068
0.043
0.026
0.128
0.051
0.154
0.070
0.149
0.028
0.089
0.362
0.039
0.030
0.035
0.296
0.037
0.053
0.017
0.184
0.023
0.099

0.0010
0.0005
0.0020
0.0007
0.0003
0.0005
0.0004
0.0004
0.0025
0.0003
0.0004
0.0004
0.0006
0.0008
0.0006
0.0005
0.0008
0.0013
0.0004
0.0015
0.0005
0.0008
0.0004
0.0005
0.0038
0.0005
0.0006
0.0003
0.0038
0.0008
0.0011
0.0005
0.0017
0.0005
0.0008

0.0010
0.0004
0.0022
0.0006
0.0002
0.0005
0.0003
0.0004
0.0017
0.0003
0.0003
0.0004
0.0003
0.0007
0.7451
0.0004
0.0006
0.0013
0.0003
0.0013
0.0004
0.0008
0.0004
0.0004
0.0038
0.0003
0.0005
0.0003
1.6069
0.0007
0.0013
0.0004
0.0014
0.0005
0.0008

0.0329
0.0148
0.0185
0.0108
0.0037
0.0124
0.0077
0.0041
0.0346
0.0020
0.0051
0.0038
0.0040
0.0066
0.0077
0.0061
0.0066
0.0434
0.0079
0.0319
0.0186
0.0207
0.0387
0.0053
0.0518
0.0232
0.0264
0.0138
0.0598
0.0101
0.0174
0.0072
0.0423
0.0057
0.0138

0.0003
0.0002
0.0007
0.0002
0.0001
0.0002
0.0001
0.0001
0.0004
0.0001
0.0001
0.0001
0.0001
0.0003
0.0001
0.0001
0.0002
0.0003
0.0001
0.0006
0.0002
0.0002
0.0002
0.0001
0.0009
0.0001
0.0002
0.0001
0.0012
0.0004
0.0006
0.0002
0.0008
0.0002
0.0002

ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
0.0002
ND
ND
0.0026
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND

0.0001
0.0014
ND
0.0004
ND
ND
0.0001
0.0005
0.0047
0.0001
0.0003
0.0003
0.0002
ND
ND
0.0001
0.0014
ND
ND
0.0159
0.0001
0.0018
0.0002
0.0005
0.0005
ND
ND
ND
ND
ND
ND
0.0005
0.0005
0.0005
ND

0.0005
0.0005
0.0011
0.0006
0.0002
0.0008
0.0003
0.0005
0.0023
0.0004
0.0006
0.0003
0.0004
0.0011
0.0008
0.0005
0.0008
0.0009
0.0006
0.0012
0.0004
0.0014
0.0003
0.0004
0.0031
0.0004
0.0004
0.0002
0.0035
0.0005
0.0009
0.0003
0.0011
0.0003
0.0007

ND = Not Detected.

3.4.2. Trace elements (V, Cr, Mn, Fe, Ni, Cu, Zn, Se)
It has been well-established that Se and Cr are often added at
low concentrations (<0.2 mg/serving size and <0.12 mg/serving
size, respectively) for nutritional purposes. This was also valid for
the samples analysed during this study.
Eleven of the 35 products for V, thirty two of the 35 products
for Cr, Mn, Cu, Se, nineteen of the 35 products for Fe, eight of the
35 products for Ni and all thirty ve products for Zn provided the
label claim (Tables 46). The content of V, Cr, Mn, Fe, Cu, Zn and
Se were within 100 15% for products MVM-46, 8, 11, 12, 14,
15, 16, 20, 21, 2427, 29, 31, 32, 34, 35. For a few other supplements, great differences were found between the calculated concentrations of V, Cr, Mn, Fe, Ni, Cu, Zn, Se and the values stated on
the label.
In products MVM-17, 13, 4, the V content was 1.61.8 times
more in comparison with label claim. In products MVM-18, 22,
the Cr content was 69.2% and 64%, respectively, whereas for
products MVM-7, 9, 15 and 17, the content was 1.32.8 times
more than the label value. For samples MVM-18, 22, the Mn
content was 62% and 51%, respectively. The Fe percent content
was only about 72%, 57% and 70% in samples MVM-19, 22 and
33, respectively, whereas in sample MVM-28 the content was
1.7 times more than the label value. One study showed that
the analysed values for Fe were considerably higher than labelled values (80190%) (Whittakar et al., 2001). The percent
content of Cu in samples MVM-1, 2, 10, 13, 22, and 26 were
75%, 57%, 71%, 72%, 51%, 75%, respectively and the Cu content
was 1.3 times more for samples MVM-17, 23, 29. The Zn percent

content for samples MVM-1, 2, 10, 13, 18, 22, 26 were found to
be 75%, 57%, 71%, 72%, 74%, 51%, and 75%, respectively, whereas
in samples MVM-17, 23, 29 the content was 1.3 times more than
the label claim. For samples MVM-3, 17, and 28, the Se content
was 1.52.0 times more than the label claim, whereas for the
samples MVM-1, 2, 18, 19, 22, 30, the percent content was
70%, 53%, 72%, 32%, 74% and 33%, respectively. Comparisons of
analysed with label values showed Se deviations from 19% to
+23% (Feifer et al., 2002) and up to 2.5 times label value (Veatch
et al., 1998) for products marketed in the United States and Canada, respectively.
3.4.3. Toxic elements (As, Pb, Cd, and Hg)
Lead, Cd, As and Hg are considered as toxic elements, therefore,
their daily involuntary intake via MVM supplements has been regulated. Estimated exposures/intakes of As, Cd, Hg and Pb were assessed with respect to safe/tolerable exposure levels described by
various national and public health organizations.
Arsenic and Cd exposures are well below the minimum risk levels of 21 and 14 lg/day, respectively (Table 2). The 35 MVM products contain As, Pb and Cd in the range from 0.6 to 15.9, 15.9 to 0.1
and 0.3 to 3.8 lg/day, respectively. Mercury was not detected in 33
products and in two products (MVM-22, 25) the content was 0.2
and 2.6 lg/day, respectively. Dolan, Nortrup, Bolger, and Capar
(2003), surveyed a variety of dietary supplement products, which
found to contain small amounts of Pb and Cd (Dolan et al., 2003).
The daily dosage was not large for these MVM supplements analysed and the total amount of these metals ingested did not exceed

B. Avula et al. / Food Chemistry 127 (2011) 5462

the safe daily exposure limit. The highest concentrations found

were As at 15.9 lg/day in MVM-22, Cd at 3.8 lg/day in MVM-29,
Hg at 2.6 lg/day in MVM-25, and Pb at 15.9 lg/day in MVM-20.
The solid and liquid supplements (MVM-24, 7, 13, 18, 2023,
25, 2731, 33) contained smaller amounts of toxic elements,
although these supplements listed many whole food components
and various botanicals that might be a source of contaminants (Table 7).
3.4.4. Other elements [Al, Co, Rb, Sr, Cs, Ba, Tl, U]
The other elements, namely Al, Co, Rb, Sr, Cs, Ba, Tl, U, were
found in the range from 0.024% to 2.41 mg/serving size, 0.001%
to 0.018 mg/serving size, 0.001% to 0.17 mg/serving size, 0.017%
to 0.36 mg/serving size, 0.0002% to 0.75 mg/serving size, 0.002%
to 0.06 mg/serving size, 0.0001% to 0.0159 mg/serving size,
0.0002% to 0.0035 mg/serving size, respectively in 35 MVM products. Note that daily intake of these elements is not regulated,
and hence label claims do not include these elements (Table 7).
4. Conclusion
Microwave digestion followed by analysis using CRC ICP-MS
with an integrated octopole system has been shown to be a simple, fast reliable method for the multi-element determination in
multivitamin/mineral dietary supplements. A study of 35 popular
MVM dietary supplements revealed that composition and levels
varied among products, and no standard compositional prole/
formulation of MVM existed. The described method shows higher recoveries of all elements of interest. The analysis showed
four toxic elements, essential and non essential elements that
can be toxic at higher concentrations were used. Three of the
35 products have calculated Cr and Se daily intake concentrations more than 150% higher than their corresponding claimed
values. On the other hand, 22, 12, 7, 20, 20, 27 and 11 products
have 1030% lower Mg, K, Cr, Mn, Cu, Zn and Se calculated daily
intake concentrations than their corresponding claimed values,
respectively. Among the seven products that report Na concentrations, three of them have less (2030%) content than the
claimed value, while one product contain higher than 30%. A total of 18 products reporting Fe concentrations, 13 of them have
less (1030%) than their claimed value, while the others have
higher (1030%) values. Among the 11 products reporting V contents, 10 products have higher value (1030%), while one product has 13% less than the claimed value. Similarly, 13 products
have higher Ca (1030%) concentrations than the claimed value,
while three products have less (1030%) value. The results revealed that all 35 products have calculated daily intake of As,
Cd, Pb and Hg concentrations lower than those of the regulatory
limits. Overall, the percentage deviation from the label claim is
element specic.

Acknowledgements
This research is supported in part by Science Based Authentication of Dietary Supplements and Botanical Dietary Supplement
Research funded by the Food and Drug Administration grant numbers 5U01FD002071-09 and 1U01FD003871-01, and the United
States Department of Agriculture, Agricultural Research Service,
Specic Cooperative Agreement No. 58-6408-2-0009.
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