D-903

Conversion Factors used in Analytical Determinations and New Product Formulation

Section D — Laboratory Operations and Specifications Revision 2 7 pages

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1.0 Purpose

The purpose of this procedure is to outline the numerical conversions required to the convert

units of concentration for strength test results into the units required for evaluation of product
label claims. Additionally, this procedure may assist in the development of new products to

ensure that the product formulation contains an appropriate quantity of raw material to meet the

label claim. This procedure helps to ensure compliance with regulatory requirements and
consistency in labelling of dietary supplements.

2.0 Scope

This procedure applies to the determination of vitamins including A, B1, B2, B3, B5, B6, B7,

B9, B12, C, D, and E in the QC laboratory at Ion Labs. This procedure applies to the formulation

of new products in the R&D laboratory at Ion Labs.

3.0 Responsibility

3.1 It is the responsibility of QC Chemists and R&D formulators to follow this procedure.

Buk It is the responsibility of QC Laboratory Management and R&D Management to
implement this procedure and to ensure that the procedure is being followed.

3.3 It is the responsibility of QC Laboratory Management and/or Analytical Development to
keep the procedure current with lon Labs practices.

4.0 Definitions

4.1 QC — Quality Control

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4.2 R&D -— Research and Development

4.3. NLT—No Less Than

4.4 DFE — Dietary Folate Equivalents

4.5 RAE- Retinol Activity Equivalents

4.6 FP - Finished Product

4.7. Vitamin A — A lipid soluble group of related organic compounds with a long carbon
chain consisting of at least four conjugated double bonds often terminating in a ring. The

vitamin A content of dietary supplements is expressed on the label as retinol activity
equivalents (RAE).

4.8 Vitamin B1 — Thiamine (also called thiamin, a water soluble vitamin).

4.9 Vitamin B2 — Riboflavin and riboflavin-5-phosphate (a water soluble vitamin).

4.10 Vitamin B3 — Niacin (also called nicotinic acid, a water soluble vitamin). Niacinamide
is another form of Vitamin B3 with identical vitamin activity to niacin. The amino acid

tryptophan is a precursor for niacin synthesis, and therefore, can also be used to supply

Vitamin B3 in dietary supplements.

4.11 Vitamin B5 — Pantothenic acid (a water soluble vitamin). Vitamin B5 is most commonly

supplied as calcium-D-pantothenate in dietary supplements as the calcium salt is more
stable than pantothenic acid and easier to work with.

4.12 Vitamin B6 — A group of chemically similar water soluble compounds which can be
interconverted in biological systems. Often supplied in the form of pyridoxine

hydrochloride or pyridoxal-5-phosphate in dietary supplements.

4.13 Vitamin B7 — Biotin (a water soluble vitamin).

4.14 Vitamin B9 — A water soluble vitamin with multiple forms which are collectively
referred to as folate. Most often supplied as folic acid or methyltetrahydrofolate in dietary

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supplements. The vitamin B9 content of dietary supplements is expressed on the product

label as dietary folate equivalents (DFE).

4.15 Vitamin B12 — A class of water soluble vitamins referred to as cobalamins. Common

forms in dietary supplements include methylcobalamin and cyanocobalamin.

4.16 Vitamin C — Ascorbic acid (a water soluble vitamin and antioxidant).

417 Vitamin D — A group of lipid soluble secosteroids. Commonly supplied as
cholecalciferol or ergocalciferol in dietary supplements.

4.18 Vitamin E — A group of lipid soluble compounds that includes tocopherols and
tocotrienols. Often supplied as esterified forms (tocopherol acetate or tocopherol

succinate) in dietary supplements due to their decreased susceptibility to oxidation

relative to tocopherol.

4.19 Vitamin K — A group of related lipid soluble compounds which differ in the number of

double bonds and length of the side chain. Two common forms in dietary supplements
are menaquinone-4 (MK-4) and menaquinone-7 (MK-7).

5.0 References

5.1 Code of Federal Regulations, 21CFR 109.9 (c) (8) (iv)

5.2. US Food and Drug Administration, Converting Units ofMeasure for Folate, Niacin, and

Vitamins A, D, and E on the Nutrition and Supplement Facts Labels: Guidance for
Industry, August 2019.

5.3 National Institutes of Health - Office Of Dietary Supplements,
https://dsid.od.nih.gov/conversions.php (accessed 12/07/22), Dietary Supplement

Ingredient Database — Unit Conversions

6.0 Conversion Factors in Analytical Determinations

6.1 Determine the label claim of the product being tested (Table 1 - first column).

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6.2 Determine the raw material used to supply the label claim in the finished product (Table

1 - second column).

6.3 Perform the analytical determination.

6.3.1 In general, the reference standard used should be the same chemical form as the
raw material used in the finished product.

6.3.2 Thiamine HCl and thiamine mononitrate reference standards may be used
interchangeably.

6.3.3. Pyridoxine and pyridoxine HCl reference standards may be used
interchangeably.

6.4 Determine the conversion factor (Table 1 - third column).

6.4.1 In the case of an analytical determination for Vitamin B1 or B6 where the

reference standard is not the same chemical form as the raw material used in the

finished product, use the conversion factor in Table 1 that corresponds to the
reference standard used (not the raw material used in the finished product).

6.5 Multiply the result of the analytical determination by the conversion factor. This is often
performed within the chromatographic software by using a multiplier.

6.6 Example 1: The product contains pyridoxine HCI with a label claim of 0.5 mg vitamin
B6. Strength testing is performed by HPLC using pyridoxine HCl reference standard, and

the result is 0.7 mg per dosage unit. The conversion factor for pyridoxine HC] is 0.823.

Therefore, the amount of vitamin B6 in the product is 0.7 mg x 0.823 = 0.576 mg or
115% of label claim.

6.7. Example 2: The product contains thiamine mononitrate with a label claim of 1.5 mg of
vitamin Bl. Strength testing is performed using thiamine hydrochloride reference

standard, and the result is 2.3 mg per dosage unit. The conversion factor for thiamine HCI

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is 0.787. Therefore, the amount of vitamin B1 in the product is 2.3 mg x 0.787 = 1.81 mg

or 121% of label claim.

7.0 Conversion Factors in Product Formulation

7.1 Determine the label claim of the product being tested (Table 1 - first column).

7.2 Determine the raw material used to supply the label claim in the finished product (Table

1 - second column).

7.3 Determine the conversion factor for the raw material (Table 1 — third column).

7.4 Determine the purity of the raw material from the raw material manufacturers certificate

of analysis or by estimation if a source for the raw material has not yet been identified.

7.5 Determine the desired overage for the raw material.

7.6 Determine the amount of raw material required to be added to the product.

7.6.1. Divide the label claim by the purity factor in decimal format.

7.6.2 Multiply the result of 7.7.1 by the overage in decimal format.

7.6.3. Divide the result of 7.7.2 by the conversion factor.

7.7. Example 3: The product has a label claim of 0.6 mg Vitamin A. Retinyl palmitate with a
purity of NLT 7.5% will be used to supply Vitamin A in the finished product with an

overage of 40%. The amount of raw material needed for the formulation is 0.6 mg + 0.075

x 1.4+ 0.546 = 20.5 mg.

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Table 1: Conversion Factors for Evaluating Label Claims and New Product Formulation

Label Claim Raw Material used in FP Conversion Factor
Retinol 1
Vitamin A Retinyl Acetate 0.872
(RAE) Retinyl Palmitate 0.546
B-Carotene 0.5
ae Thiamine HCI 0.787
bec Thiamine Mononitrate 0.811
yp Riboflavin 1
Vieni Be Riboflavin-5-Phosphate 1

Nicotinic Acid 1
Niacinamide 1
Vitamin B3 Tryptophan 0.0167
Niacinamide Ascorbate j
Inositol Nicotinate 0.911
Vitamin BS Calcium-D-Pantothenate 0.920
Pyridoxine 1

Vitamin B6 Pyridoxine HCl 0.823
Pyridoxal-5-Phosphate 1
Vitamin B7 Biotin 1
Folic Acid 1.7
Vitamin B9 Calcium-DL-5-Methyltetrahydrofolate 1.7
(DFE) Calcium-L-5-Methyltetrahydrofolate 1.7
L-5-Methyltetrahydrofolate 1.7
a Cyanocobalamin 1
Vineet BE Methylcobalamin 1

Ascorbic Acid 1
Vitamin C Ascorby] Palmitate 0.425
Niacinamide Ascorbate *
Pe Cholecalciferol 1
emi Ergocalciferol 1
D-a-Tocopherol (RRR-a-Tocopherol) 1
DL-a-Tocopherol 0.5

, DL-a-Tocopherol Acetate 0.5
Vitamin © D-a-Tocopheol Acetate 1
DL-a-Tocopherol Succinate 0.5
D-a-Tocopherol Succinate 1
Vitamin K1 (phylloquinone) 1
Vitamin K Vitamin K2 (menaquinone)
Vitamin MK-4 (menaquinone-4)
Vitamin MK-7 (menaquinone-7) 1

* For formulating finished product: consult raw material CoA for vitamin B3/C content;
for analytical testing: use multiplier of 1 with either niacinamide or ascorbic acid standard

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8.0 Revision History

| Rev | Date | Description of Changes | CCR # | By |
|-----|----------|------------------------|-------|----|
| 0 | 12/20/22 | New procedure. N/A S. Sassman | - | - |
| 1 | 01/17/24 | Add conversion factors for additional vitamers. CC- | 24-0024 | S. Sassman |
| 2 | 05/06/24 | Add conversion factor for ascorbyl palmitate CC- | 24-0188 | S. Sassman |